Photosensitive ganglion cells: A diminutive, yet essential population | Archivos de la Sociedad Española de Oftalmología (English Edition)

array:24 ["pii" => "S2173579420302401" "issn" => "21735794" "doi" => "10.1016/j.oftale.2020.06.020" "estado" => "S300" "fechaPublicacion" => "2021-06-01" "aid" => "1813" "copyright" => "Sociedad Española de Oftalmología" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Arch Soc Esp Oftalmol. 2021;96:299-315" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0365669120303476" "issn" => "03656691" "doi" => "10.1016/j.oftal.2020.06.032" "estado" => "S300" "fechaPublicacion" => "2021-06-01" "aid" => "1813" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Arch Soc Esp Oftalmol. 2021;96:299-315" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "Revisión" "titulo" => "Células ganglionares fotosensibles: una población diminuta pero esencial" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "299" "paginaFinal" => "315" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Photosensitive ganglion cells: A diminutive, yet essential population" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1479 "Ancho" => 1740 "Tamanyo" => 691252 ] ] "descripcion" => array:1 [ "es" => "A) Fotomontaje de una retina de rata adulta en la que se aprecian células ganglionares de la retina intrínsecamente fotosensibles (CGRif) marcadas con melanopsina (CGRm+), distribuidas por toda la retina. B) Mapa de vecinos de la misma retina (A) que muestra la distribución topográfica de las CGRm+, que se contabilizaron manualmente, un total de 2.683. Escala de color del mapa de vecinos en la que cada color representa un incremento de 4 vecinos en un radio de 0,22mm y oscila desde púrpura (0-6 vecinos) a rojo oscuro (42-48 vecinos). C y D) Detalles a mayor aumento en los que se aprecia el marcaje de las CGRif, tanto en sus somas celulares como en sus extensas dendritas en el plano de foco. Barra: A:=1mm, C:=50μm, D=25μm; I: inferior; N: nasal; S: superior; T: temporal." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "B. Vidal-Villegas, A. Gallego-Ortega, J.A. Miralles de Imperial-Ollero, J.M. Martínez de la Casa, J. García Feijoo, M. Vidal-Sanz" "autores" => array:6 [ 0 => array:2 [ "nombre" => "B." "apellidos" => "Vidal-Villegas" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Gallego-Ortega" ] 2 => array:2 [ "nombre" => "J.A." "apellidos" => "Miralles de Imperial-Ollero" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "Martínez de la Casa" ] 4 => array:2 [ "nombre" => "J." "apellidos" => "García Feijoo" ] 5 => array:2 [ "nombre" => "M." "apellidos" => "Vidal-Sanz" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173579420302401" "doi" => "10.1016/j.oftale.2020.06.020" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420302401?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669120303476?idApp=UINPBA00004N" "url" => "/03656691/0000009600000006/v1_202106010616/S0365669120303476/v1_202106010616/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173579420302486" "issn" => "21735794" "doi" => "10.1016/j.oftale.2020.06.025" "estado" => "S300" "fechaPublicacion" => "2021-06-01" "aid" => "1811" "copyright" => "Sociedad Española de Oftalmología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Soc Esp Oftalmol. 2021;96:316-20" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Short communication" "titulo" => "Visual impairment induced by prosthetic cobaltism" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "316" "paginaFinal" => "320" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Afectación visual por cobaltismo protésico" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1096 "Ancho" => 1255 "Tamanyo" => 226062 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A. Fundus within normal range. B. Computerized campimetry showing visual field retraction in both eyes." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "B.F. Sánchez-Dalmau, F. Spencer, L. Sánchez-Vela, A. Camós-Carreras, S. Nogué Xarau, J.A. Fernández-Valencia" "autores" => array:6 [ 0 => array:2 [ "nombre" => "B.F." "apellidos" => "Sánchez-Dalmau" ] 1 => array:2 [ "nombre" => "F." "apellidos" => "Spencer" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Sánchez-Vela" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Camós-Carreras" ] 4 => array:2 [ "nombre" => "S." "apellidos" => "Nogué Xarau" ] 5 => array:2 [ "nombre" => "J.A." "apellidos" => "Fernández-Valencia" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669120303452" "doi" => "10.1016/j.oftal.2020.06.030" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669120303452?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420302486?idApp=UINPBA00004N" "url" => "/21735794/0000009600000006/v1_202106040601/S2173579420302486/v1_202106040601/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173579420302528" "issn" => "21735794" "doi" => "10.1016/j.oftale.2020.09.004" "estado" => "S300" "fechaPublicacion" => "2021-06-01" "aid" => "1824" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Soc Esp Oftalmol. 2021;96:293-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Management of strabismus related to infantile glaucoma: Case series" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "293" "paginaFinal" => "298" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Manejo del estrabismo asociado al glaucoma de la infancia: serie de casos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 355 "Ancho" => 900 "Tamanyo" => 35770 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Patient number 5. Exotropia in patient with glaucoma secondary to trauma in left eye, with low visual acuity and multiple glaucoma surgeries in that eye." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "N. Güemes Villahoz, L. Morales Fernández, C. Narváez Palazón, M.N. Moreno, M.R. Gómez de Liaño Sánchez" "autores" => array:5 [ 0 => array:2 [ "nombre" => "N." "apellidos" => "Güemes Villahoz" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Morales Fernández" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Narváez Palazón" ] 3 => array:2 [ "nombre" => "M.N." "apellidos" => "Moreno" ] 4 => array:2 [ "nombre" => "M.R." "apellidos" => "Gómez de Liaño Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669120303592" "doi" => "10.1016/j.oftal.2020.09.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669120303592?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420302528?idApp=UINPBA00004N" "url" => "/21735794/0000009600000006/v1_202106040601/S2173579420302528/v1_202106040601/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Photosensitive ganglion cells: A diminutive, yet essential population" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "299" "paginaFinal" => "315" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "B. Vidal-Villegas, A. Gallego-Ortega, J.A. Miralles de Imperial-Ollero, J.M. Martínez de la Casa, J. García Feijoo, M. Vidal-Sanz" "autores" => array:6 [ 0 => array:4 [ "nombre" => "B." "apellidos" => "Vidal-Villegas" "email" => array:1 [ 0 => "beatrizvidalvillegas@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Gallego-Ortega" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "J.A." "apellidos" => "Miralles de Imperial-Ollero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "J.M." "apellidos" => "Martínez de la Casa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "J." "apellidos" => "García Feijoo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "M." "apellidos" => "Vidal-Sanz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Oftalmología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Oftalmología, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria (IMIB) Virgen de la Arrixaca. El Palmar, Murcia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Células ganglionares fotosensibles: una población diminuta pero esencial" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2487 "Ancho" => 2925 "Tamanyo" => 1377491 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A) Photomontage of an adult rat retina showing intrinsically photosensitive retinal ganglion cells (RGCif) marked with melanopsin (RGCm+), distributed throughout the retina. B) Adjacency map of the same retina (A) that shows the topographic distribution of the RGCm+, which were counted manually, a total of 2,683. Colour scale of the adjacency map in which each colour represents an increase of 4 adjacents within a radius of 0.22mm and ranges from purple (0-6 adjacents) to dark red (42-48 adjacents). C and D) Details with a greater increase in which the marking of the RGCif can be seen, both in their cellular somas and in their extensive dendrites in the focus plane (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article). Bar: A:=1mm, C:=50μ m, D=25μ m; I: lower; N: nasal; S: upper; T: temporary." ] ] ] "textoCompleto" => "The retinaOne of the main functions of the retina, that of obtaining light information from our environment, is carried out by photoreceptors, neurons full of visual pigments and specialised for phototransduction, i.e. capturing electromagnetic energy (wavelengths within the visible spectrum) and converting it into electrical energy. The capture of a photon by the visual pigments induces a change in the molecule that activates a G-protein which, in turn, sets in motion an intracellular cascade that ends in a transitory change in the membrane potential of the photoreceptor, a hyperpolarisation, a signal that serves as an interneuronal communication and is transmitted to other neurons in the retina for further processing. In addition, the retina has the function of comparing light signals detected by the photoreceptors and producing response patterns that can range from basic information about the level of environmental illumination to the image pattern detected by a single photoreceptor in the foveal region; a region of the retina specialised for our fine vision that determines our spatial and temporal visual acuity as well as our ability to see colours.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> The retina is capable of performing these functions by adapting to illumination intensities in the range of 10 logarithmic units and, despite changing ambient light intensity, maintains the same appearance of the objects we see.Imaging and non-imaging pathsThe information sent by the retina is responsible on the one hand for the formation of images (FI) for our conscious visual perception of the world around us and, on the other hand, for non-image-forming visual functions (NFI) which nevertheless have important implications for our physiology and daily behaviour.The vast majority of our retinal ganglion cells (RGC) work for the FI of our visual environment, i.e. our conscious visual perception, the location and perception of shapes, their texture, colour, movement and perspective. In humans and primates, approximately 90% of RGCs go to the geniculated nucleus of the thalamus, the most important central relay station of visual information before they go to the striated visual cortex, the first working station in the arduous elaboration of our conscious visual perception.Another group of slightly less than 10% of RGCs are dedicated to reflex maintenance tasks, of which we are not aware but which also contribute to FI and are fundamental to our vision, such as eye movements when faced with a new visual scene or the stabilisation of a moving visual scene, or to accommodate and converge in front of nearby objects or to focus on distant objects. All the nuclei that participate in FI generally have a topographic representation of the surface of the retina or retinotopic map.Finally, in humans and primates there is a very small percentage of RGCs that express the melanopsin photopigment and use the intensity of environmental light (irradiance) to regulate behavioural and physiological functions the circuits of which do not form images and have no relation to the conscious perception of vision. These functions are collectively referred to as the NFI visual functions. They enable the body to set the time of our central circadian clock and to anticipate changes in the environment by modifying its behaviour, and to regulate the photomotor reflex.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Many additional behaviours also depend on the level of environmental lighting, such as regulation of metabolic homeostasis,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> melatonin synthesis,<a class="elsevierStyleCrossRef" href="#bib0010">2</a> our mood and cognitive abilities,<a class="elsevierStyleCrossRef" href="#bib0020">4</a> body temperature,<a class="elsevierStyleCrossRef" href="#bib0025">5</a> induction of sleep and alertness,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> masking of motor activity and aversion to light,<a class="elsevierStyleCrossRef" href="#bib0035">7</a> or exacerbation of migraine and photophobia.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>Although the knowledge we have today about our FI functions comes mostly from studies conducted in the visual system of primates and humans,<a class="elsevierStyleCrossRef" href="#bib0005">1</a> most of the knowledge we have today about the NFI visual functions comes from studies conducted in rodents, mainly in mice, by the tools that have been made available for their identification and distinction from the other RGC.<a class="elsevierStyleCrossRefs" href="#bib0010">2,9–11</a> The use of techniques of genetic and molecular engineering has allowed the advance of our knowledge on the visual system of the mouse up to the point that it is at present the sensory system that is better known and surprisingly it is much more similar to that of the primate than we thought. This paper reviews current concepts about the melanopathic pathway and its functions, obtained from recent studies carried out mainly in mice. We will also make a brief mention of the alterations of the melanopsynic pathway in some diseases.Retinal ganglion cellsThe information processed in the retina is transmitted to the brain encoded in a train of nerve impulses by the RGC axons, the only ones whose axons leave the retina and which account for a tiny proportion of retinal neurons. For example, in the adult rodent, RGCs do not reach 1% of the retinal neuron population.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Currently, according to morphological, physiological, topographical, molecular and innervation territory criteria, it is thought that there are up to 40 different types of RGC.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Each one of these includes particular aspects of the visual scene that are transmitted in parallel to subcortical regions that perform specific tasks.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> In the mouse, up to 46 different subcortical targets have been described.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>Inherently photosensitive retinal ganglion cellsGeneral characteristics of intrinsically photosensitive retinal ganglion cellsRGCs that are dedicated to NFI visual functions constitute a very small proportion (in humans ≈1% and in rodents ≈3%, see below). These cells are characterised by the expression of the melanopsin pigment (encoded by the Opn4 gene), which transduces light into electrical signals, hence they are called melanopsinic (RGCm+), intrinsically photosensitive (RGCif), photosensitive or third retinal photoreceptor.<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a> Melanopsin takes its name from the melanophores in the skin of the frog where it was discovered,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> shortly after RGCifs were observed in monkeys and mice<a class="elsevierStyleCrossRefs" href="#bib0080">16,19</a> and in the human retina.<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> RGCifs in rodents and humans express 2 neurotransmitters, glutamate and the polypeptide activator of pituitary adenylate cyclase (PACAP).<a class="elsevierStyleCrossRef" href="#bib0110">22</a> RGCifs are depolarized in response to light stimulation of melanopsin, even in the absence of information from cones and rods, and also in vitro.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> The elimination of melanopsin expression results in an attenuation of circadian synchronisation and photomotor reflex,<a class="elsevierStyleCrossRef" href="#bib0115">23</a> and the elimination of functional photoreception of the 3 photoreceptors (rods, cones and RGCif)<a class="elsevierStyleCrossRef" href="#bib0120">24</a> or genetic ablation of RGCifs<a class="elsevierStyleCrossRefs" href="#bib0125">25,26</a> causes the loss of visual NFI functions, demonstrating that the origin of this melanopsynic pathway is in RGCif.The first RGCifs described were the M1.<a class="elsevierStyleCrossRefs" href="#bib0080">16,19,27</a> A few years later, it was documented that RGCifs also projected into brain regions responsible for FI, such as the superior colliculus (SC) (quadrigeminal tuber in humans) and the dorsal nucleus of the lateral geniculate (dorsal geniculate nucleus in humans), both in humans<a class="elsevierStyleCrossRef" href="#bib0105">21</a> and in mice.<a class="elsevierStyleCrossRefs" href="#bib0140">28,29</a> In mice (rd/rd cl), which do not have cones or rods but do have RGCif, crude visual behaviour could be observed that resolved visual patterns and detected contrasts.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> Later, it was documented that most of the RGCif afferences to the dorsal division of the lateral geniculated nucleus (LGNd) came from the M4,<a class="elsevierStyleCrossRef" href="#bib0150">30</a> which were soon identified as RGC α-ON sustained with high contrast sensitivity.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> More recently, 2 additional RGCifs with projection to the LGNd and possible contribution to spatial vision have been identified, i.e., the M5, which exhibits opposing colour responses<a class="elsevierStyleCrossRef" href="#bib0160">32</a> and the M6.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> The contribution of RGCifs to spatial vision has been characterised in mice<a class="elsevierStyleCrossRef" href="#bib0170">34</a> and humans, where they appear to contribute to the perception of brightness, spatial vision and increased image appearance.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> At present, six different types of RGCifs have been described in rodents, which are called M1-M6 and are distinguished on the basis of their morphological characteristics, size of their soma, extension and stratification of their dendritic tree, level of melanopsin expression, intrinsic and extrinsic responses, characteristics of their peripheral receptor fields, regions of the brain to which they project and specific markers.<a class="elsevierStyleCrossRefs" href="#bib0085">17,28,30,32</a>,<a class="elsevierStyleCrossRefs" href="#bib0165">33,36–40</a>Number and distribution of intrinsically photosensitive retinal ganglion cellsIn adult rodents, the Brn3a marker, a Pou4f1 transcription factor, can be used to identify the vast majority of conventional RGCs representing ≈96% of RGCs.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> As the vast majority of Brn3a+RGCs do not express melanopsin and viceversa, the joint use of both markers allows to study in parallel but independently these 2 populations of RGCs under normal conditions and against different types of lesions.<a class="elsevierStyleCrossRefs" href="#bib0210">42–52</a> In rats, the population of RGCif constitutes approximately 2.5-2.7% of the total population of RGC in albino and pigmented retinas<a class="elsevierStyleCrossRefs" href="#bib0085">17,27,41–43,49,53,54</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Similarly, the use of Brn3b, another Pou4f2 transcription factor, and melanopsin as cellular markers makes it possible to identify a small subpopulation of RGCif M1 Brn3b- and distinguish it from the vast majority of M1s and all other M2-M6s which are Brn3b+.<a class="elsevierStyleCrossRefs" href="#bib0275">55,56</a> In the pigmented mouse, the total number of RGCifs has varied from 1,02157 2,05829 to 2,57036. These variations are due to the methodology used to identify RGCifs, differences in the type of anti-melanopsin antibody, immunohistochemical technique, use or not of signal amplifiers or transgenic animals that express a marker in the melanopsin locus.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> In rodents, melanopsin expression is regulated by both light and retinal circadian rhythms<a class="elsevierStyleCrossRefs" href="#bib0290">58–60</a> and in mice, 2 isoforms of melanopsin has been described, one long (Opn4L) and one short (Opn4S), which is expressed 40 times more than the long one.<a class="elsevierStyleCrossRefs" href="#bib0305">61,62</a> M1 and M3 express both (Opn4S and Opn4L), while M2 and M4 only express Opn4L. Of the different subtypes, M1-M3 constitute the majority of RGCifs and are the easiest to identify as they express more melanopsin, while M430,<a class="elsevierStyleCrossRef" href="#bib0315">63</a> M5<a class="elsevierStyleCrossRef" href="#bib0320">64</a> and M6<a class="elsevierStyleCrossRef" href="#bib0165">33</a> express melanopsin in very small quantities and are very difficult to identify with standard immunohistochemical techniques, without amplification. Currently, it is accepted that RGCif constitute ≈3% of mouse RGC.<a class="elsevierStyleCrossRefs" href="#bib0200">40,65</a>The distribution of RGCifs differs; almost all cellular subtypes (except M3) tessellate the retina, M1 and M2 are more abundant in the upper hemirretin, M5 are abundant in the lower hemirretin and M4 have a naso-temporal gradient with maximum densities in the super-temporal region.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>General projections of intrinsically photosensitive retinal ganglion cellsRGCif projections have been studied in detail with techniques that increase the visibility of melanopsin or that use markers inserted in the melanopsin locus. For example, replacing the melanopsin gene with the sequence encoding tau-LacZ, a protein composed of the enzymeβgalactosidase, linked to a tau signal sequence (an actin-associated protein that facilitates antegrade transport through the axon to the axonal terminal) Opn4tauLacZ (Hattar<a class="elsevierStyleCrossRef" href="#bib0085">17</a>, 2002). Immunohistochemical signal amplification techniques, such as recombinant Cre29 or green fluorescent protein expression, have also been used. Axonal projections can be identified with the intravitreal injection of an adeno-associated virus (AAV) that transfects the human placental alkaline phosphatase gene (AAV-fles-plap) into transgenic mice expressing Cre under the melanopsin promoter (Opn4Cre29,66).Of the 46 subcortical territories that innervate the RGC, 30% lack innervation of the RGCif.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> In general, RGCifs project to the basal prosencephalon and hypothalamus, the thalamus and habenula region, the midbrain and the accessory optical system (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). In the basal prosencephalon they innervate the preoptic areas (lateral, medial and ventrolateral), the perisupraoptic nucleus, the subparaventricular zone (sPVZ), the suprachiasmatic nucleus (SCN), the anterior and lateral regions of the hypothalamus and the regions of the amygdala (anterior, medial and central), as well as the nucleus of the terminal striae bed. In the thalamus and the region of the habenula, the perihabenular nucleus (PHb), the LGNd and the ventral lateral geniculated nucleus (LGNv), the intergeniculated leaflet and the zona incerta are innervated. In the midbrain they innervate the pretectal olive nucleus (PON), the anterior, medial and posterior pretectal nuclei, and the nucleus of the optical tract. In addition, they innervate the visual layers of the SC, the periaqueductal grey substance and the nuclei of the accessory optical system (dorsal, lateral and medial terminal nuclei).<a class="elsevierStyleCrossRefs" href="#bib0020">4,10,11,66–70</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>To summarise, it could be said that most M1 and the rest of the RGCifs (M2-M6) are Brn3b+, projecting to the dorsal nucleus of the geniculate and SC, are capable of mediating crude spatial vision in the absence of rod and cone function and of mediating contrast sensitivity (M4) or colour vision (M5), while the M1Brn3b- project exclusively to circadian centres.<a class="elsevierStyleCrossRef" href="#bib0340">68</a>Morphological characteristics and projections of intrinsically photosensitive retinal ganglion cellsThe M1These were the first to be identified, they settle in the RGC layer but can appear displaced in the nuclear internal (NI) (M1d); their number is around 980 per retina and the size of the cellular soma is one of the smallest (14−16μ m).<a class="elsevierStyleCrossRefs" href="#bib0080">16,29,30,36</a>,<a class="elsevierStyleCrossRef" href="#bib0200">40</a> An M1d has been described, called interneurone melanopsinic, as it lacks an axon in the optic nerve.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> The dendritic tree of M1 is hardly branched, extending in the outermost part of the OFF subslice of the IP (S1) with a diameter of ≈300−350 μm<a class="elsevierStyleCrossRefs" href="#bib0145">29,30</a> and performs synapses en passant with ON bipolar axons type 6 and with dopaminergic amacrines. During development, a small proportion of M1 and M1d extend their dendrites also to the PE (external retinal dendrites) and there they associate with axonal terminals of the cones, are called biplexiform RGCifs and contribute to the stratification of the retina and lamination of the cones.<a class="elsevierStyleCrossRefs" href="#bib0355">71,72</a> In mice and monkeys, a small subgroup of M1 has been described with axonal collaterals that end in PI<a class="elsevierStyleCrossRefs" href="#bib0365">73,74</a> and contribute to the regulation of the adaptation of the retina to light through its connections with dopaminergic amacrines.<a class="elsevierStyleCrossRef" href="#bib0370">74</a> M1s show little spontaneous activity in the dark and their intrinsic response is very sensitive to light, exhibiting rapid and wide ranging responses. M1s exhibit extrinsic ON responses to light that are small and sustained.M1s project approximately 15 brain targets involved in classical NFI visual functions.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> One of the main targets is the SCN, a ≈1mm pair nuclei located above the chiasma with a nuclear zone receiving direct retinal afference from the retino-hypothalamic tract and a cortical zone with neurons acting as circadian oscillators. The main retinal afference to the SCN comes from the M1 and to a lesser extent from the M2.<a class="elsevierStyleCrossRef" href="#bib0375">75</a>GCRifs can be differentiated according to the brn3b expression in RGC M1Brn3b- and RGCBrn3b+. The population of RGCif M1Brn3b- (about 200) innervates the SCN and is sufficient to synchronize the circadian rhythm, because when RGCifM1Brn3b+are genetically eliminated, most NFI functions are abolished, but circadian synchronization persists.<a class="elsevierStyleCrossRef" href="#bib0275">55</a> The SCN in turn innervates areas involved in mood (ventral tegmental and raphe area) and cognitive functions (hippocampus). These areas can be influenced through the SCN or directly through a direct pathway of RGCif axons to these nuclei, the medial amygdala and the perihabenular nucleus (PHb), respectively.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Both the M1Brn3b- and M1Brn3b+project both to the interniculate leaflet and the ventral NGLv region, which are nuclei in charge of prolonging the period of circadian rhythms.<a class="elsevierStyleCrossRef" href="#bib0340">68</a> The M1Brn3b+RGCifs profusely innervate midbrain nuclei unrelated to circadian rhythms, nuclei of the thalamus and hypothalamus. The cortex of the PON, involved in the control of the pupil reflex to light,55 is innervated by RGCif M1Brn3b+68, while the nuclear region is primarily innervated by non-M1Brn3b+RGCif. RGCifM1Brn3b+project to the PHb nucleus through the retino-perihabenular pathway, a recently described pathway formed by some 76 RGCif M1 Brn3b+that directly mediate the effects of light on mood.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>The M2M2s have their somas in the GRC layer, are discreetly larger than the M1 (16−19μ m) and their number is around 830 per retina.<a class="elsevierStyleCrossRefs" href="#bib0145">29,30,40</a> The dendritic tree stratifies in the internal sub-layer (ON) of the IP with a diameter of ≈316−324μ m and with more regular branches than the M1.<a class="elsevierStyleCrossRefs" href="#bib0145">29,30</a> They receive afferences of the bipolar ON cone cells type 8, contain significantly less melanopsin than M1 and have a sensitivity to light of an order of magnitude lower than M1. Their extrinsic response is of the broad and sustained ON type, and their receptor field has the classic antagonistic peripheral centre structure.M2 projects typical NFI subcortical regions, innervates the SCN and innervates the central region of the PON profusely. They also innervate FI regions, such as NGLd.<a class="elsevierStyleCrossRefs" href="#bib0050">10,29</a>The M3M3s are characterised by being biostratified, having one of the largest dendritic tree (457−497μ m) and extend into both sub-layers of the IP; their somas (17−19μ m) sit on the RGC layer and represent less than 10% of the RGCif. The membrane properties and intrinsic responses to light stimulation of M3 are similar to those of M2. The extrinsic responses of M3, similar to those of M2, show a robust response of the ON pathway that induces cellular depolarization.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> This cellular type is scarce and does not form a mosaic that envelops the retina,<a class="elsevierStyleCrossRef" href="#bib0180">36</a> a necessary criterion to consider a different subtype of RGC.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>The fate of the M3 projections is not exactly known although it has been suggested that they project the SC<a class="elsevierStyleCrossRef" href="#bib0380">76</a> and PHb<a class="elsevierStyleCrossRef" href="#bib0020">4</a> nuclei.The M4M4s are very sensitive to contrast, they sit in the RGC layer and their shadows are the largest of all RGCifs (19−24 μm). Their dendritic, radial and highly branched trees grow on the temporonasal axis (210−420μ m)<a class="elsevierStyleCrossRefs" href="#bib0155">31,77</a> and are distributed following a naso-temporal gradient, with a maximum in the super-temporal region. The monostratified dendritic tree in the ON subslice of the IP, discreetly more external than the M2, and probably receives afferences from bipolar cone terminals type 7.<a class="elsevierStyleCrossRefs" href="#bib0150">30,31</a> M4 lack immunofluorescence against melanopsin detectable with standard techniques, but when the signal is amplified a clear cellular marking appears.M4 have intrinsically weak responses that vary according to light adaptation; weak retinal response adapted to light, but greater in adaptation to darkness.<a class="elsevierStyleCrossRef" href="#bib0390">78</a> This intrinsic response of melanopsin contributes to increasing the excitability of the cell and would cause the M4 to fire at very low luminous intensities.<a class="elsevierStyleCrossRef" href="#bib0315">63</a> In knockout mice (Opn4-) that do not express melanopsin, deficits in contrast sensitivity due to the lack of melanopsin in M431 can be observed.The M4 presents extrinsic responses conducted by cones, with large receptor fields organized in center-ON antagonistic periphery-OFF, reminiscent of conventional RGC fields, with sensitivity to movement but without directional selectivity. Recently, it has been documented that when they are recorded adapted to light they present colour opposition, like the M5.<a class="elsevierStyleCrossRef" href="#bib0385">77</a>M4 correspond to the classical sustained RGCα -ON and express non-phosphorylated high molecular weight neurofilaments, osteopontin and calbindin, as well as low levels of melanopsin.<a class="elsevierStyleCrossRefs" href="#bib0385">77,79</a> They can be identified by the co-location of non-phosphorylated high molecular weight neurofilaments and calbindine, with SMI32 antibodies and anti-calbindine (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). In transgenic mice expressing melanopsin witness with a green fluorescent protein, an average of 570 SMI32+/retin was counted and classified as RGCif M4 (Schmidt et al.,<a class="elsevierStyleCrossRef" href="#bib0155">31</a> 2014).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>M4s overwhelmingly innervate the LGNd ventromedial sector and mediate contrast sensitivity in the absence of cones and rods. In the presence of cones and rods, they also contribute to visual acuity and object tracking.<a class="elsevierStyleCrossRefs" href="#bib0140">28–31,78</a>The M5M5s are cells with chromatic opposition which have their soma (12−16μ m) in the GRC layer, with highly branched and compact dendritic trees (149−274μ m) which stratify in the ON subslice of the IP.<a class="elsevierStyleCrossRefs" href="#bib0150">30,32,77</a> They present very weak intrinsic responses, less than the M4. Their immunoreactivity against melanopsin is barely detected with standard techniques and when the signal is amplified, markings can be seen in the soma, but not in the dendrites. M5 have sustained extrinsic ON-type responses, at least an order of magnitude greater than the intrinsic ones. Their particular characteristic is their ultraviolet-green chromatic opposition; the receptor field is constructed so that they have a centre with selective afference of UV cones (through cone bipolars type 9) and mixture of UV and M cones (through cone bipolars types 6, 7 and 8), and a strong suppressive periphery dominated by M cone afferences through gabaergic amacrines.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> As with other RGCifs, scotopic responses are probably mediated by rod bipolars, AII amacrines (primary pathway) and rod-cone coupling (secondary pathway of the rods).The M5 project to the LGNd and thus can provide chromatic signals to the visual cortex,32 but it is thought that they can also innervate the PON and the other nuclei innervated by M6. In addition, they project to the intergenic tab which in turn projects to the SCN, suggesting a pathway for M5 to provide chromatic information to the spectral opposition neurons of the SCN.<a class="elsevierStyleCrossRef" href="#bib0400">80</a>The M6M6s are spiny bistable cells that settle in the RGC layer. Both the soma (11−15μ m) and its highly branched dendritic tree (190−250μ m) are the smallest of all RGCifs. In retinas of pigmented Cdh3-GFP transgenic mice a few dozen M6 RGCifs were counted, a figure that may underestimate the real magnitude of this subtype since in this mouse they are only marked in the ventral retina.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> The external dendritic branch extends to the distal margin of the IP, close to the NI, where they stratify the M1 and the external tree of the M3. The internal dendritic branch accounts for approximately 85% of the dendritic volume and extends to the internal margin of the IP.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> M6 express very low levels of melanopsin detectable with tyramid amplification techniques and when staining appears it can be observed as patches in the soma region, but not in dendrites. M6 have very weak intrinsic responses, which are lower than M4 and M5. The M6 have sustained ON-type responses when their entire relatively small and strongly antagonistic centre-periphery receptor field is illuminated. Although they have part of their dendritic tree in the OFF region of the IP, their responses are, like those of all RGCifs, of the sustained ON type. It is thought that the external dendritic tree receives in the OFF subslice of the IP ectopic afferences en passant of bipolar axons ON. These cells lack colour response and directional selectivity.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>On the one hand, the M6 projects to typical NFI territories such as the centre of the PON, the pretectal posterior nucleus, the intergeniculated leaflet and NGLv and, on the other hand, projects weakly to the NGLd.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>Inherently photosensitive retinal ganglion cells in primates and humansIn humans, the total number of RGCif varies between 0.2,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> 0.4,<a class="elsevierStyleCrossRef" href="#bib0405">81</a> 0.8<a class="elsevierStyleCrossRefs" href="#bib0100">20,62,82</a> and 1.5%<a class="elsevierStyleCrossRef" href="#bib0415">83</a> of the RGC population.<a class="elsevierStyleCrossRef" href="#bib0420">84</a> These variations are due to technical differences in detecting melanopsin, as well as to the lower expression of melanopsin in M2 and M4, compared with M1. As in rodents, melanopsin is expressed in a more abundant short isoform, present in M1 and M3, and a long isoform present in all melanopsins.The somas and dendritic trees of the RGCm+of the retinas of humans and macaques are among the largest. Initially, these RGCifs were classified according to their stratification in the OFF and ON subslices of the IP into external and internal RGCifs, respectively.<a class="elsevierStyleCrossRefs" href="#bib0105">21,59,81,82</a> More recently, using antibodies against the N and C terminals of human melanopsin, Hannibal et al.<a class="elsevierStyleCrossRef" href="#bib0310">62</a> (2017), based on the location and size of the soma and on the stratification of their dendritic trees, classified RGCifs according to the nomenclature used in rodents. The predominant type in humans is M1, with a high proportion of displaced cells (dM1) and with higher expression of melanopsin. One type of giant M1 (GM1), which projects the nGDL, exhibits an opposing response to the yellow-ON blue-OFF colour, mediated by S-OFF cones antagonized by a cone response (L+M)-ON,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> involving recently described amacrine cells that receive from bipolar S-ONcones.<a class="elsevierStyleCrossRef" href="#bib0425">85</a> Displaced giants GM1d were also identified. Some of the M1s had axonal collaterals that extended into the retina. The M2s (known as internal) are less abundant and express less melanopsin. In humans, there are also RGCifs similar to M3s that stratify at S1 and S5, but their frequency is very small and their characterisation very poor.<a class="elsevierStyleCrossRefs" href="#bib0310">62,82</a> They have also been described in M4 humans, distributed in the naso-temporal axis and with higher density in the temporal hemiretina.<a class="elsevierStyleCrossRef" href="#bib0410">82</a> To date it is not known whether the human and primate retina has M5 and M6.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> The distribution of M1 in humans contrasts with that of M1 in rodents, since in humans and primates they have very high densities in the central perifoveal region and lower densities in the periphery, whereas M2 are less abundant and are distributed similarly to M4.<a class="elsevierStyleCrossRefs" href="#bib0310">62,84</a> This different density of RGCif in the perifoveal and peripheral region may mean a different function in the perception of colour opposition.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>In the primate, RGCif projections have been studied by combining a very sensitive antegrade tracer, the choleric B toxin subunit and immunohistochemistry to reveal the presence of PACAP.<a class="elsevierStyleCrossRef" href="#bib0430">86</a> The presence of PACAP+terminals was documented in regions supporting visual NFI functions. Thus, primate RGCifs densely project the SCN, PON and pregeniculate complex (which corresponds to the intergeniculate tab of the rodent). In the pretectal region, they also showed dense innervation in the nucleus of the optical tract but scarce innervation in the posterior medial pretectal nucleus. Doubly marked fibres have also been observed in regions supporting visual functions FI, the brachium of the SC and the visual layers of the SC, as well as in lateral geniculated nucleus in the corresponding contralateral (1, 4 and 6) or ipsilateral (2, 3 and 5) layers, in the main regions (parvo or magno) but not in the koniocellular ones.<a class="elsevierStyleCrossRef" href="#bib0310">62</a>Contribution of intrinsically photosensitive retinal ganglion cells to non-image-forming visual functionsIn mice, ablation of RGCifs<a class="elsevierStyleCrossRefs" href="#bib0125">25,26,87</a> causes the loss of NFI visual functions with maintenance of classic vision and conventional RGCifs, indicating that RGCifs constitute the functional unit of the NFI system, which transmits to the brain the information obtained from both classic photoreceptors and melanopsin activation.<a class="elsevierStyleCrossRef" href="#bib0440">88</a> The NFI functions consist mainly of 1) the daily synchronisation of our circadian rhythms; 2) regulation of the photomotor reflex; 3) regulation of our sleep-wake rhythms; 4) regulation of body temperature; 5) regulation of metabolic activity; 6) regulation of our cognitive abilities and mood; 7) aversion to light; and 8) adaptation of the retina to light.Synchronisation of circadian rhythmsThe synchronisation of our circadian rhythms consists in the timing of our central circadian pacemaker, located in the SCN, which receives direct information from the retina through the retino-hypothalamic tract, mainly innervated by RGCif M1. All the species studied have circadian rhythms (which oscillate in a period of 24h; circa=approximate; day=24h) governed by a main pacemaker, which imposes its own rhythm even in constant light conditions, but which is delayed a little every day. These pacemakers are synchronised with time keys and in our case sunlight acts as a timer to set our circadian pacemaker on time. The synchronisation of the circadian rhythm depends on a subpopulation of 200 M1Brn3b-4, and disappears in animals that lack the retino-hypothalamic tract.<a class="elsevierStyleCrossRef" href="#bib0445">89</a>Circadian synchronisation directly modulates the rhythms of many physiological functions such as appetite, temperature cycles and the level of circulating hormones, which in turn synchronises clocks present in many tissues of the body.<a class="elsevierStyleCrossRef" href="#bib0450">90</a> In addition to regulating circadian rhythms, the SCN also acts as a relay station to conduct light information to other territories that receive direct input from the RGCif, thus providing an indirect pathway for functions related to sleep/wakefulness, our cognitive abilities and mood. The secretion of melatonin, which modifies our cardiac rhythms, and the suppression of motor activity are examples of this concept; although they are regulated in a circadian way, they are also suppressed in an acute way by exposure to light (known as masking),<a class="elsevierStyleCrossRef" href="#bib0190">38</a> an effect mediated by direct afference to the ventral nucleus of the sub-ventricular zone,<a class="elsevierStyleCrossRef" href="#bib0335">67</a> and it is thought that the same RGCifs that innervate the SCN are responsible for both behaviours.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>Pupillary reflex to lightOne of the classic NFI functions is the regulation of the pupillary reflex to light by the PON innervated in its cortex by the M2 and other non-M1Brn3b+RGCifs and in its centre by M1Brn3b+RGCifs. The photomotor reflection is performed by the 3 types of photoreceptors. Typical rapid and broad responses at the beginning of the stimulus depend on cones and rods, while sustained responses following acute responses depend on melanopsin. This has been documented in mice lacking cones and rods (rd/rd cl), which had slow but durable responses, coming from RGCifs, and in knock-out mice (Opn4-/-) lacking intrinsic melanopsin-mediated responses<a class="elsevierStyleCrossRef" href="#bib0115">23</a> that had rapid transient responses, with no response to high irradiances.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> In triple knock-out mice, which do not express melanopsin and have altered phototransduction of rods and cones (Gnat1-/-; Cnga3-/-; Opn4-/-), a normal retina is observed, but total absence of pupillary response to light, circadian compliance, suppression of motor activity or any other of the typical NFI functions triggered by light.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Similar results were obtained from mice in which RGCif had been genetically ablated.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> In humans, the contribution of the different photoreceptors has been examined using chromatic pupillometry which quantifies the photomotor reflex based on the spectral sensitivity of each photoreceptor; the different components of this reflex have been described.<a class="elsevierStyleCrossRef" href="#bib0455">91</a> After the presentation of light a phasic response is produced, of rapid appearance and short duration, with a robust contraction of the pupil mediated by rods and cones. Subsequently, the pupil gradually relaxes to a more dilated state and if the intensity of light exceeds the melanopsin activation threshhold, the pupil remains contracted to a constant size, this response is called the post-phase response. If the light has been maintained for more than 3min, when the light is switched off the pupil constriction persists for a few seconds before relaxing to normal values, and this is called the post-lighting pupil response (PLPR), which is melanopsin-dependent.<a class="elsevierStyleCrossRefs" href="#bib0335">67,91,92</a> The PLPR are added binocularly when the stimulus is presented binocularly<a class="elsevierStyleCrossRef" href="#bib0465">93</a> and do not appear to be directly influenced by colour.<a class="elsevierStyleCrossRef" href="#bib0470">94</a>Sleep/Wake rhythmsIt was thought that sleep-wake cycles were regulated indirectly through our circadian rhythms, but it has been documented that Brn3b+RGCifs send direct intrinsic and extrinsic information to the lateral hypothalamus region and ventrolateral preoptic area to regulate both the onset and duration of the sleep cycle.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6,67,95</a> It is not yet known exactly which of the 6 types of RGCif Brn3b+is responsible for the regulation of these rhythms, but it has been suggested that it would be the M1 or M2 that express the highest levels of melanopsin.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>Body temperature rhythmsBody thermoregulation follows circadian rhythms and its control has been attributed to the function of the central pacemaker of the SCN. Today we know that the SCN performs circadian control of body temperature with the afferent information that reaches it through the M1Brn3b- RGCifs, but that the Brn3b+RGCifs are necessary for direct acute control of body temperature; for example, after the presentation of a night-time light pulse. Brn3b+RGCifs are thought to exert their effect through direct projections to the preoptic median and ventrolateral nuclei of the hypothalamus.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>Regulation of metabolic activityThe daily metabolic activity is adapted to the circadian rhythms imposed by the light-darkness cycles. This activity is controlled by hypothalamic nuclei containing pacemakers which are in turn regulated by the central pacemaker of the SCN. In mice with selective hypomorphic Pitx3 expression, where the retino-hypothalamic tract is absent, there is a mismatch between the SCN pacemakers (responsible for circadian rhythms) and the ventromedial hypothalamus (responsible for energy intake and balance rhythms) resulting in behavioural and metabolic alterations that affect locomotor activity, feeding and energy expenditure rates, and corticosterone secretion.<a class="elsevierStyleCrossRef" href="#bib0445">89</a> These alterations are thought to be due to the lack of maturation of the SCN pacemaker during development due to the lack of retinal afferences.<a class="elsevierStyleCrossRefs" href="#bib0280">56,89,96</a>Mood and cognitive abilitiesThe effect of light in the modulation of our moods and intellectual capacity is well known. For example, a flight that crosses several time zones decouples our circadian rhythm from solar time (jet lag) and takes a few days to become regularized. During these days, we experience alterations in our sleep/wake rhythm, cognitive deterioration, discomfort and irritability that disappear when our circadian rhythm is again in step with local solar time. This type of alteration is also experienced by workers who run shifts (alternating day/night shifts), at night, or in those who suffer from seasonal affective disorder that appears in late autumn and during the winter as a result of the rapid shortening of daylight hours.<a class="elsevierStyleCrossRef" href="#bib0325">65</a> Classically, it was thought that both the regulation of cognitive functions and mood depended on SCN. Today it is known that SCN indirectly influences these functions,65 but that there are 2 different RGCifs projections directly responsible for these functions. On the one hand, a subpopulation of approximately 71 RGCif M1Brn3b+that innervate the thalamic nucleus PHb (retinal-habdominal pathway) is directly responsible for the modulation of mood.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Furthermore, these RGCifs that inervate the nucleus PHb emit collaterals that project to the dorsal and ventral striatum and to the prefrontal cortex. All of these nuclei are involved in the control of affective-emotional processes, mood and depression, and mood regulation and depressive disorders, respectively.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>On the other hand, the M1Brn3b RGCifs― (approximately 200) that innervate the SCN are responsible for the modulation of cognitive abilities, independently of the synchronisation of the circadian rhythm,<a class="elsevierStyleCrossRef" href="#bib0020">4</a> although the innervated nuclei responsible for these abilities are unknown. For example, mice lacking RGCif M1Brn3b+showed normal cognitive and learning functions in tests of recognition of new objects and the Morris water labyrinth, thus documenting that the absence of this subpopulation does not affect the cognitive functions of these animals since they are mediated by RGCif M1Brn3b-.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>Aversion to lightLight aversion, i.e. the distant displacement of light,<a class="elsevierStyleCrossRef" href="#bib0485">97</a> is a reflex sensory response that is observed in neonatal mice as soon as P6, a period in which the only sensitivity to light is produced by the activation of RGCifs, long before signals from cones and rods begin to be produced and sent to the RGCifs. In Opn4-/- neonatal mice no light aversion is seen, indicating that melanopsin is necessary for light aversion.<a class="elsevierStyleCrossRef" href="#bib0490">98</a> This behaviour is mediated by the SC,<a class="elsevierStyleCrossRef" href="#bib0495">99</a> so it is probable that it is due to the afferences of the RGCif not M1, since they are the only ones that innervate the SC at these postnatal ages.<a class="elsevierStyleCrossRef" href="#bib0500">100</a>Adaptation of the retina to lightA small population of RGCif M1 Brn3b- has intraretinal axonal collaterals that project to the external retina,<a class="elsevierStyleCrossRefs" href="#bib0365">73,74</a> transmitting luminance signals through the dopaminergic system and thus influencing the adaptation of the retina to light, enabling it to operate at illumination levels comprising 10 logarithmic units. The M1 excitation signal causes the secretion of dopamine by dopaminergic amacrines<a class="elsevierStyleCrossRefs" href="#bib0370">74,101</a> which form an intraretinal feedback pathway transmitting cone, rod and RGCif signals in a centrifugal direction from the inner to the outer retina. The released dopamine exerts its action through D1-D5 dopamine receptors and the activation of these modifies retinal circuits according to the prevailing lighting; that is, electrical decoupling through the retina, modulating the glutamate exciter receptors in the horizontal ones and regulating the activity of the sodium channels of the RGC and bipolar channels. The depletion of dopamine in the retina results in an alteration in the adaptation of our vision to light.<a class="elsevierStyleCrossRef" href="#bib0510">102</a>Contribution of intrinsically photosensitive retinal ganglion cells to visual image-forming functionsThe discovery of new RGCif subtypes in mice and primates that projected the LGNd and SC, nuclei directly involved in FI and conscious visual perception, suggested the participation of RGCif in FI visual functions. Gnat1-/-; Cnga3-/- mice, which lack functional rods and cones and depend on melanopsin for light detection, showed gross visual behaviours which required approximately twice as much time as control mice to pass visual tests.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> These visual abilities disappeared in triple knock-out mice (Gnat1-/-; Cnga3-/-; Opn4-/-), which lacked any kind of functional photoreception.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> Subsequent studies have documented that mice lacking in melanopsin (Opn4-/-)<a class="elsevierStyleCrossRef" href="#bib0140">28</a> or lacking in CFRif M4 (Opn4Cre/+; Bnr3bzDTA/+ mice)<a class="elsevierStyleCrossRef" href="#bib0275">55</a> show deficits in contrast sensitivity both in subcortical (optokinetic tracking) and cortical (visual water labyrinth)<a class="elsevierStyleCrossRef" href="#bib0515">103</a> behavioural visual tasks, showing that the melanopsin in these cells influences their physiological properties.<a class="elsevierStyleCrossRef" href="#bib0155">31</a>It is now accepted that RGCifs contribute to contrast detection,<a class="elsevierStyleCrossRef" href="#bib0155">31</a> light intensity discrimination,<a class="elsevierStyleCrossRef" href="#bib0140">28</a> adaptation of LGNd activity according to irradiance<a class="elsevierStyleCrossRefs" href="#bib0140">28,104</a> and spatial pattern coding.<a class="elsevierStyleCrossRefs" href="#bib0050">10,34</a> Using techniques to present images that independently modulate the visibility of melanopsin vs. cones and rods, evoked responses of LGNd were recorded in control animals of which 20% responded to patterns visible only by melanopsin. Melanopsin signals have sufficient spatial-temporal resolution to encode spatial patterns, a modest spatial resolution with receptor fields from ≈13° and a modest temporal frequency ≈1Hz.<a class="elsevierStyleCrossRef" href="#bib0170">34</a>The colour of light in circadian synchronisationThe synchronisation of the circadian rhythms to the light/darkness cycles not only takes into account the information on oscillations in light intensity, but also its colour variations. As twilight develps there is a progressive enrichment of short wave light. This is due to the filtering of long wavelength light by the Chappuis band of the ozone layer (Chappuis filter effect) when the sun is below the horizon, at a time of day when the sky is particularly blue (the blue hour) and which is observed both at the end of twilight and at the beginning of dawn.<a class="elsevierStyleCrossRef" href="#bib0525">105</a> In the SCN, ≈25% of the neurons recorded intracellularly are sensitive to spectral changes with cone-dependent opposite colour responses, most with blue-ON/yellow-OFF responses and a minority with yellow-ON/blue-OFF responses.<a class="elsevierStyleCrossRef" href="#bib0400">80</a> The light colour information allows the SCN to obtain accurate information about the time of transition, twilight or dawn, and thus to achieve a more reliable time setting of the circadian pacemaker as well as allowing the SCN to distinguish a decrease in irradiance because the sky has become cloudy, from the decrease that occurs at dusk or dawn.<a class="elsevierStyleCrossRef" href="#bib0530">106</a> It has been postulated that the use of colour to accurately determine the onset of phase change of our circadian rhythms could be an evolutionarily conserved strategy and perhaps one of the original purposes of colour vision.<a class="elsevierStyleCrossRef" href="#bib0400">80</a> In rodents, it has been suggested that the M5, characterized by its chromatic opposition, could inform the SCN of spectral variations through its afferences to the intergeniculate tongue.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> In primates, chromatic RGCif GM1 (blue-OFF/yellow-ON)21 has been described and recently it has been documented that this information could be mediated by the afferences of the bipolar S-ON cone to a new amacrine cell that receives excitatory afferences from the bipolar S-ON cone and, in turn, makes inhibitory contacts in RGCif M1 resulting in a blue-OFF85 response. These RGCif M1 with S-OFF responses of primates could be the SCN afference for the tuning of the circadian clock setting at dawn and dusk, when the highest colour contrasts of light occur.<a class="elsevierStyleCrossRef" href="#bib0425">85</a>Non-image-forming visual functions in the diseaseClinical studies carried out on neurodegenerative diseases have documented alterations in the melanopathic pathway associated with anomalies in visual functions NFI82,84. Thus, patients with Parkinson's disease exhibit a significant decrease in the RGCif population that could be responsible for the alterations in mood and sleep/wake cycles reported in these patients.<a class="elsevierStyleCrossRef" href="#bib0535">107</a> Similarly, in retinas of older donors (> 70 years) a decrease in RGCif density and atrophy of their dendritic trees was observed that could also be related to alterations in circadian rhythms observed in the elderly.<a class="elsevierStyleCrossRef" href="#bib0540">108</a> In a study carried out on the retinas of patients with Alzheimer's disease, degeneration of RGCif and alterations in their dendritic trees were documented, and these findings were correlated with alterations in circadian functions.<a class="elsevierStyleCrossRef" href="#bib0545">109</a> In a study carried out on completely blind patients with total absence of light perception due to different causes (retinitis pigmentosa, retinopathy of prematurity, retinopathies due to retinitis or rubella syndrome, congenital glaucoma, neuropathy or optic neuritis, or unknown causes) it was documented that a small fraction of these (≈33%) showed suppression of melatonin secretion when exposed to light, suggesting the preservation of circadian rhythms and the persistence of the retinohypothalamic tract. This observation was, however, absent in the 3 patients of the study that had undergone bilateral enucleation.<a class="elsevierStyleCrossRef" href="#bib0550">110</a> Another study examined the prevalence of circadian alterations in 123 blind women without or with light perception, studying alterations in sleep/wakefulness rhythms and the rhythm of melatonin secretion by examining the sleep/wakefulness diary of these patients, as well as the urinary excretion every 4−8hours of 6-sulfatoximelatonin, the main urinary metabolite of melatonin. Most of the participants without any perception of light (≈63%) had abnormalities in their circadian rhythms or were not in sync. These were patients with bilateral enucleations or retinopathy of prematurity. The majority of participants with light perception (≈69%) had normal circadian rhythms and were patients with retinitis pigmentosa or age-related macular degeneration.<a class="elsevierStyleCrossRef" href="#bib0555">111</a>Visual functions of intrinsically photosensitive retinal ganglion cells in the postnatal periodIn rats and mice, RGCifs are present in the retina from birth (P0) and show photosensitive responses long before the cones and rods begin to function and send their signals to the retina, which roughly coincides with the eye opening (P10). RGCifs were identified and classified in records made in the postnatal retina (P10-12) according to their latency, sensitivity and intensity of response to light at 3 types: I, the most frequent 78%; II (15%) and III (13%).<a class="elsevierStyleCrossRef" href="#bib0560">112</a> Electrophysiological records and the combined use of anti-melanopsin antibodies and SMI32 (an antibody against the high molecular weight non-phosphorylated subunit of the neurofilaments triplet) have allowed the classification of these postnatal RGCifs and their association with adult types. Thus, type I (m+SMI32+), II and III (m+SMI32−) RGCifs correspond to M4, M2 and M1, respectively.<a class="elsevierStyleCrossRefs" href="#bib0480">96,113</a> These RGCifs decrease both in number and in photosensitivity during early postnatal development until adulthood, which is mainly due to the reduction and death of melanopsin M4 RGCifs expression.<a class="elsevierStyleCrossRef" href="#bib0570">114</a>The functions of RGCifs during early postnatal development are 1) to regulate the development of the pattern of vascular branching in the retina and the regression of the embryonic hyaloid vasculature; mice lacking melanopsin (Opn4-/-) show abnormal vascular development and hyaloid regression<a class="elsevierStyleCrossRef" href="#bib0575">115</a>; 2) the aversion to light of neonatal mice (P6)<a class="elsevierStyleCrossRefs" href="#bib0035">7,98</a>; 3) the inter-RGCif coupling necessary to produce the waves of spontaneous retinal activity<a class="elsevierStyleCrossRef" href="#bib0580">116</a> that regulate the refinement of ocular segregation of axonal retinal terminals in the geniculate and SC; the M1 Brn3b- RGCifs regulate the triggering properties of RGCs through signals by their intraretinal axonal collaterals<a class="elsevierStyleCrossRef" href="#bib0280">56</a>; 4) the maturation of the circadian rhythm, i.e. the establishment of the duration of the circadian rhythm phases; the subgroup of 200 RGCif M1Brn3b− which exclusively projects the SCN, is responsible for the maturation of the circadian clock and the initial establishment of the duration of the phases<a class="elsevierStyleCrossRefs" href="#bib0280">56,96,117</a> and 5) the organisation of the retinal architecture and the lamination of the cones. Opn4DTA/DTA mice lacking RGCif showed a disorganisation of the cones at P7 and P16, and an anomalous displacement of these to other layers of the retina. In these mice it was documented that light during the first postnatal week contributes to restrict the somas of the cones to the external nuclear and influences the lamination of the cones to their layer. It has been postulated that in these mice the RGCif use their external dendrites to communicate with the cones and regulate the number of cones displaced outside the NE.<a class="elsevierStyleCrossRef" href="#bib0360">72</a>Melanopsin phototransductionOpsins are receptors coupled to a G-protein that convert the energy of a photon into a change of the membrane potential. Visual pigments consist of an apoprotein (the opsin) to which a chromophore molecule, a derivative of vitamin A1, 11-cis-retinaldehyde, is attached. Small changes in the structure of the protein change the absorption spectrum. Melanopsin is a visual pigment with a λmax of 480nm.The efficiency of melanopsin is comparable to cone and stick opsins, but there are differences between melanopsin phototransduction and classical opsins: 1) phototransduction in cones and rods results in a transient hyperpolarisation and, as a consequence, the signal transmitted in the synaptic foot is a reduction of glutamate release; the phototransduction cascade of melanopsin is more similar to that of invertebrates and results in membrane depolarisation (Graham et al.,<a class="elsevierStyleCrossRef" href="#bib0590">118</a> 2008) and consequently there is an increase in the frequency of action potentials dependent on ambient lighting<a class="elsevierStyleCrossRefs" href="#bib0345">69,119</a>; 2) the melanopsin phototransduction cascade is much slower<a class="elsevierStyleCrossRef" href="#bib0600">120</a>; 3) RGCifs lack cellular specialisations (discs and saccules) that have rods and cones to optimise the chances of capturing a photon, resulting in a difference in molecule density/unit area of 8.300 times greater in cones and rods with respect to RGCifs and, therefore, less probability of absorption of one photon per photo-stimulation area for RGCifs.<a class="elsevierStyleCrossRef" href="#bib0345">69</a> However, melanopsin can be activated in scotropic conditions, which confers great sensitivity to the melanopsin system<a class="elsevierStyleCrossRef" href="#bib0605">121</a>; 4) the amplification of the melanopsin phototransduction cascade compensates for the low amount of melanopsin and the few photons that are absorbed; once the melanopsin activation threshold is reached, the response persists during long periods of constant illumination; it has been documented in in vitro studies that the melanopsin signal can remain active for 10 continuous hours of light<a class="elsevierStyleCrossRef" href="#bib0610">122</a>; 5) regeneration of the visual pigment is thought to occur by a light-dependent mechanism; photo-exposed melanopsin is converted to metamelanopsin which retains the chromophore in the all-trans form and after absorption of a new photon regenerates the 11-cys form, thus RGCifs do not discolour regardless of how much light they are exposed to; these are called bistable pigments because they have an intrinsic regeneration mechanism that makes them resistant to discolouration, similar to invertebrates.<a class="elsevierStyleCrossRefs" href="#bib0460">92,123</a> It is not known whether Müller cells act as a chromophore reservoir for melanopsin,<a class="elsevierStyleCrossRef" href="#bib0505">101</a> and 6) it was thought that melanopsin phototransduction employed similar mechanisms in all RGCifs and that those expressing little melanopsin (M4-M6) owed their primary function to their extrinsic afferences, relegating the function of their small amount of melanopsin to second place. However, it has been documented that the intracellular melanopsin cascade uses different mechanisms in different types of RGCif<a class="elsevierStyleCrossRef" href="#bib0315">63</a> and that in RGCifs involved in FI functions melanopsin, although low, can modulate the processing of signals from rods and cones. For example, increasing the contrast sensitivity of M4s involved in spatial vision in a range of lighting from very high to very low levels involving only rods, using potassium permeable channels to increase the excitability of M4.<a class="elsevierStyleCrossRef" href="#bib0315">63</a>Final considerationsRGCifs are characterised by their intrinsic response to melanopsin, but they also have extrinsic responses mediated by classical photoreceptors through the same circuits as conventional RGCifs, so that the melanopsin pathways integrate all the light signals captured by the retina. So, why do RGCis want these integrated afferences? One possible explanation would be to extend their range of action, since they inform the brain of very faint light signals (which activate the rods), moderate (in which the cones with a faster kinetic signal participate and also inform about colour), up to very high and maintained levels (which activate the melanopsin).Is the classification of RGCif according to its NFI and FI functions still valid? The classification of RGCifs as responsible for NFI visual functions has been useful to study these functions in detail, but as more has been learned about these cells it has become clear that the original division in RGCifs responsible for NFI and FI functions is not as clear. Many M1Brn3b+ RGCifs project nuclei responsible for NFI (e.g., PON) and FI (e.g., LGNd regions) vision functions. Even a single subpopulation of RGCif M1Brn3b- that is primarily devoted in adults to NFI (circadian rhythm synchronisation) visual functions, during early to mid postnatal development, however, refinement of FI visual functions (axonal segregation in the LGNd) and NFI visual functions (such as establishment of the time period of circadian rhythms)56. Schematically, this classification could be summarised in that the M1Brn3b− have primarily NFI functions related to circadian rhythms, while the M1Brn3b+ have mostly non-circadian NFI functions with a very small contribution to FI functions; the M2, also Brn3b+, would be responsible for NFI visual functions (the photomotor reflex) and FI visual functions, while the M3-M6, all Brn3b+, would be mostly responsible for FI visual functions.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Could we ignore a RGCif population as small as the M4-M6? The mammal's brain in general has very little redundancy. However, and neural populations that may seem insignificant perform crucial functions. For example, we know that as few as about 70 M1Brn3n+ RGCifs form the retino-perihabenular pathway and are responsible for mood, which is substantially modified by irregular exposures to light during normal day/night cycles.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Furthermore, it has recently been documented that the melanopsin in RGCif M4 is able to modulate its excitability in a very wide range of lighting conditions, increasing its sensitivity to contrast. This effect is produced in M4 cells by a mechanism never before associated with melanopsin, consisting of the closure of potassium leakage channels (potassium channels of the TASK subfamily, of the double pore domain potassium channel family, K2P), which is selective from the RGCifs involved in FI (Sonoda et al.,<a class="elsevierStyleCrossRef" href="#bib0315">63</a> 2018). As this mechanism is not present in M1, it has been suggested that the melanopsin phototransduction cascade would act with different mechanisms on different types of RGCif. Melanopsin would be able to enhance the visual signal of M4 RGCifs, which encode FI, in a range of luminance that vary from a dim light that activates only rods to a more intense light that preferentially activates cones, thus modulating visual processes in much greater ranges than previously thought.<a class="elsevierStyleCrossRef" href="#bib0315">63</a>In short, RGCifs have many features that distinguish them from the more conventional RGCifs: 1) RGCifs perform a wide range of functions; to the increasingly well understood NFI functions we must add the knowledge of the FI functions performed by M4, while the exact role of M5 and M6 has yet to be deciphered; 2) RGCifs express very different amounts of melanopsin, high in M1, moderate with an order of magnitude lower in M2-3, or barely noticeable with 2 orders of lower magnitude in M4-6. However, independently of the amount of melanopsin, their expression confers on them a very particular functional singularity; 3) in general, RGCs functionally respond to light stimuli depending on the sublaminate of the IP in which they extend their dendrites, external (a, OFF) or internal (b, ON), so that RGCs that branch out in the external or internal sublaminate have responses of centre-OFF (decrease of discharges in the presence of light) or centre-ON (increase of discharges in the presence of light), respectively.<a class="elsevierStyleCrossRef" href="#bib0620">124</a> However, RGCif M1, M3 and M6, in spite of extending their dendrites in the OFF sublaminamte, have the peculiarity that their responses are of the ON type, as the rest of the RGCifs. These are produced because M1, M3 and M6 receive in the OFF subslice ectopic afferences en passant of bipolar ON, which has led to think that this region of the IP could be considered an additional subdivision of the OFF subslice that informs the RGCif ON, and 4) finally, and although it has not been the subject of this review, the RGCif exhibit particular resilience to multiple types of retinal injury that makes them particularly resistant to injuries.<a class="elsevierStyleCrossRefs" href="#bib0210">42,43,45,49</a> In summary, it is therefore a type of RGCif, one of the 40 possible types, which is actually composed of 6 subtypes, which still has many unknown issues and will undoubtedly continue to contribute to maintain the melanopsynic system as one of the most active fields of research in vision.FundingThis work has been party financed by the Seneca Foundation, Science and Technology Agency Region of Murcia (19881/GERM/15) and by the Ministry of Economy and Competitiveness, Carlos III Health Institute, European Regional Development Fund “a way of making Europe” (SAF2015-67643-P; PID 2019-106498GB-I00; RD16/0008/0004; RD16/0008/0016).Conflict of interestNo conflict of interest was declared by the authors." "textoCompletoSecciones" => array:1 [ "secciones" => array:19 [ 0 => array:3 [ "identificador" => "xres1520846" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1379101" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1520845" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1379100" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "The retina" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Imaging and non-imaging paths" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Retinal ganglion cells" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Inherently photosensitive retinal ganglion cells" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "General characteristics of intrinsically photosensitive retinal ganglion cells" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Number and distribution of intrinsically photosensitive retinal ganglion cells" ] ] ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "General projections of intrinsically photosensitive retinal ganglion cells" ] 9 => array:3 [ "identificador" => "sec0040" "titulo" => "Morphological characteristics and projections of intrinsically photosensitive retinal ganglion cells" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "The M1" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "The M2" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "The M3" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "The M4" ] 4 => array:2 [ "identificador" => "sec0065" "titulo" => "The M5" ] 5 => array:2 [ "identificador" => "sec0070" "titulo" => "The M6" ] 6 => array:2 [ "identificador" => "sec0075" "titulo" => "Inherently photosensitive retinal ganglion cells in primates and humans" ] ] ] 10 => array:3 [ "identificador" => "sec0080" "titulo" => "Contribution of intrinsically photosensitive retinal ganglion cells to non-image-forming visual functions" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Synchronisation of circadian rhythms" ] 1 => array:2 [ "identificador" => "sec0090" "titulo" => "Pupillary reflex to light" ] 2 => array:2 [ "identificador" => "sec0095" "titulo" => "Sleep/Wake rhythms" ] 3 => array:2 [ "identificador" => "sec0100" "titulo" => "Body temperature rhythms" ] 4 => array:2 [ "identificador" => "sec0105" "titulo" => "Regulation of metabolic activity" ] 5 => array:2 [ "identificador" => "sec0110" "titulo" => "Mood and cognitive abilities" ] 6 => array:2 [ "identificador" => "sec0115" "titulo" => "Aversion to light" ] 7 => array:2 [ "identificador" => "sec0120" "titulo" => "Adaptation of the retina to light" ] ] ] 11 => array:3 [ "identificador" => "sec0125" "titulo" => "Contribution of intrinsically photosensitive retinal ganglion cells to visual image-forming functions" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0130" "titulo" => "The colour of light in circadian synchronisation" ] ] ] 12 => array:2 [ "identificador" => "sec0135" "titulo" => "Non-image-forming visual functions in the disease" ] 13 => array:2 [ "identificador" => "sec0140" "titulo" => "Visual functions of intrinsically photosensitive retinal ganglion cells in the postnatal period" ] 14 => array:2 [ "identificador" => "sec0145" "titulo" => "Melanopsin phototransduction" ] 15 => array:2 [ "identificador" => "sec0150" "titulo" => "Final considerations" ] 16 => array:2 [ "identificador" => "sec0155" "titulo" => "Funding" ] 17 => array:2 [ "identificador" => "sec0160" "titulo" => "Conflict of interest" ] 18 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-05-21" "fechaAceptado" => "2020-06-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1379101" "palabras" => array:5 [ 0 => "Intrinsically photosensitive retinal ganglion cells" 1 => "Melanopsin retinal ganglion cells" 2 => "Retina" 3 => "M1-M6 melanopsin cells" 4 => "Non-image forming visual system" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1379100" "palabras" => array:5 [ 0 => "Células ganglionares intrínsecamente fotosensibles" 1 => "Células ganglionares melanosínicas" 2 => "Retina" 3 => "Células M1-M6" 4 => "Sistema visual no formador de imágenes" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Our visual system has evolved to provide us with an image of the scene that surrounds us, informing us of its texture, colour, movement, and depth with an enormous spatial and temporal resolution, and for this purpose, the image formation (IF) dedicates the vast majority of our retinal ganglion cell (RGC) population and much of our cerebral cortex. On the other hand, a minuscule proportion of RGCs, in addition to receiving information from classic cone and rod photoreceptors, express melanopsin and are intrinsically photosensitive (ipRGC). These ipRGC are dedicated to non-image-forming (NIF) visual functions, of which we are unaware, but which are essential for aspects related to our daily physiology, such as the timing of our circadian rhythms and our pupillary light reflex, among many others. Before the discovery of ipRGCs, it was thought that the IF and NIF functions were distinct compartments regulated by different RGCs, but this concept has evolved in recent years with the discovery of new types of ipRGCs that innervate subcortical IF regions, and therefore have IF visual functions. Six different types of ipRGCs are currently known. These are termed M1-M6, and differ in their morphological, functional, molecular properties, central projections, and visual behaviour responsibilities. A review is presented on the melanopsin visual system, the most active field of research in vision, for which knowledge has grown exponentially during the last two decades, when RGCs giving rise to this pathway were first discovered." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Nuestro sistema visual ha evolucionado para proveernos una imagen de la escena que nos rodea informándonos de su textura, color, movimiento, y profundidad con una enorme capacidad de resolución tanto espacial como temporal, y a esta finalidad, la formación de imágenes (FI) dedica la inmensa mayoría de nuestras células ganglionares de la retina (CGR) y gran parte de nuestra corteza cerebral. Por otra parte, una proporción minúscula de CGR, además de recibir información de fotorreceptores clásicos conos y bastones, expresan melanopsina y son intrínsecamente fotosensibles (CGRif). Estas CGRif se dedican a funciones visuales no formadoras de imágenes (NFI), de las que somos inconscientes, pero que resultan imprescindibles para aspectos relacionados con nuestra fisiología cotidiana como la puesta en hora de nuestros ritmos circadianos y nuestro reflejo fotomotor, entre otras muchas. Desde el descubrimiento de las CGRif se pensó que las funciones FI y NFI eran compartimentos distintos regulados por diferentes CGR, pero este concepto ha evolucionado en los últimos años con el descubrimiento de nuevos tipos de CGRif que inervan regiones subcorticales FI y por tanto presentan funciones FI. Hoy se conocen 6 tipos diferentes de CGRif que se denominan M1-M6 y difieren en sus propiedades morfológicas, funcionales, moleculares, proyecciones centrales y responsabilidades en comportamientos visuales. En este trabajo revisamos el sistema visual melanopsínico, el campo de investigación más activo en visión y cuyo conocimiento ha crecido exponencialmente durante las últimas dos décadas, desde que se descubrieron por primera vez las CGR que dan origen a esta vía." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Vidal-Villegas B, Gallego-Ortega A, Miralles de Imperial-Ollero JA, Martínez de la Casa JM, García Feijoo J, Vidal-Sanz M. Células ganglionares fotosensibles: una población diminuta pero esencial. Arch Soc Esp Oftalmol. 2021;96:299–315." ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2487 "Ancho" => 2925 "Tamanyo" => 1377491 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A) Photomontage of an adult rat retina showing intrinsically photosensitive retinal ganglion cells (RGCif) marked with melanopsin (RGCm+), distributed throughout the retina. B) Adjacency map of the same retina (A) that shows the topographic distribution of the RGCm+, which were counted manually, a total of 2,683. Colour scale of the adjacency map in which each colour represents an increase of 4 adjacents within a radius of 0.22mm and ranges from purple (0-6 adjacents) to dark red (42-48 adjacents). C and D) Details with a greater increase in which the marking of the RGCif can be seen, both in their cellular somas and in their extensive dendrites in the focus plane (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article). Bar: A:=1mm, C:=50μ m, D=25μ m; I: lower; N: nasal; S: upper; T: temporary." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1768 "Ancho" => 2925 "Tamanyo" => 1044893 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A) Photomontage of a pigmented mouse retina showing retinal ganglion cells marked with antibodies that recognise non-phosphorylated high molecular weight neurofilaments (SMI32) and calbindine. The cells marked with SMI32 correspond to the RGCα type, while those doubly marked are marked with white dots and correspond to the intrinsically photosensitive M4 RGC type. In this retina, 580 M4 RGCif were counted. Note the distribution of these cells on the nasal-temporal axis with a higher density in the super-temporal quadrant. B-D) Details at higher magnification showing the marking of the RGCifs αwith SMI32 (B), calbindine (C) and double marking of the RGCifs M4 (D). Bar: A=500μ m, B–D=50μ m; I: lower; N: nasal; S: upper; T: temporary." ] ] 2 => array:9 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Fernandez et al.,<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Duda et al.,<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Sondereker et al.,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> Delwig et al.,<a class="elsevierStyleCrossRef" href="#bib0330">66</a> Gooley et al.,<a class="elsevierStyleCrossRef" href="#bib0335">67</a> Li and Schmidt,<a class="elsevierStyleCrossRef" href="#bib0340">68</a> Do<a class="elsevierStyleCrossRef" href="#bib0345">69</a> and Lucas et al.<a class="elsevierStyleCrossRef" href="#bib0350">70</a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "The most important retinal cores of the non-image-forming NFI (bold) and image-forming FI (italic) visual functions are highlighted." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">[Main RGCif innervation areas</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prosencephalon and hypothalamus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Preoptic area (ventrolateral, lateral, medial), subparaventricular area, suprachiasmatic nucleus, perisupraoptic nucleus, anterior and lateral regions of the hypothalamus, amygdala (anterior, medial and central), nucleus of the terminal striae \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">THALAMUS and habenula \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Perihabenular nucleus, lateral dorsal geniculate, lateral ventral geniculate, intergeniculate leaflet, uncertain zone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Midbrain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Periaqueductal grey substance, pretectal olive core, pretectal nuclei (anterior, medial and posterior), nucleus of the optic tract, visual layers of the upper colliculus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Accessory optical system \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dorsal, lateral and medial terminal cores \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2614012.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main innervation territories of intrinsically photosensitive retinal ganglion cells (RGCif) in mice." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:124 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:3 [ "editores" => "H.Kolb, E.Fernandez, R.F.Nelson" "titulo" => "The Architecture of the Human Fovea" "serieFecha" => "1995" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Central projections of melanopsin-expressing retinal ganglion cells in the mouse" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.20970" "Revista" => array:6 [ "tituloSerie" => "J Comp Neurol." "fecha" => "2006" "volumen" => "497" "paginaInicial" => "326" "paginaFinal" => "349" "link" => array:1 [ …1] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Circadian physiology of metabolism" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.aah4967" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "2016" "volumen" => "354" "paginaInicial" => "1008" "paginaFinal" => "1015" "link" => array:1 [ …1] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Light Affects Mood and Learning through Distinct Retina-Brain Pathways" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2018.08.004" "Revista" => array:6 [ "tituloSerie" => "Cell." "fecha" => "2018" "volumen" => "175" "paginaInicial" => "71" "paginaFinal" => "84" "link" => array:1 [ …1] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Distinct ipRGC subpopulations mediate light’s acute and circadian effects on body temperature and sleep" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7554/eLife.44358" "Revista" => array:4 [ "tituloSerie" => "Elife." "fecha" => "2019" "volumen" => "8" "link" => array:1 [ …1] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.0808312105" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci." "fecha" => "2008" "volumen" => "105" "paginaInicial" => "19998" "paginaFinal" => "20003" "link" => array:1 [ …1] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glutamatergic Neurotransmission from Melanopsin Retinal Ganglion Cells Is Required for Neonatal Photoaversion but Not Adult Pupillary Light Reflex" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0083974" "Revista" => array:5 [ "tituloSerie" => "PLoS One." "fecha" => "2013" "volumen" => "8" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current understanding of photophobia, visual networks and headaches" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0333102418784750" "Revista" => array:6 [ "tituloSerie" => "Cephalalgia." "fecha" => "2019" "volumen" => "39" "paginaInicial" => "1623" "paginaFinal" => "1634" "link" => array:1 [ …1] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Architecture, Function, and Assembly of the Mouse Visual System" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev-neuro-071714-033842" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Neurosci." "fecha" => "2017" "volumen" => "40" "paginaInicial" => "499" "paginaFinal" => "538" "link" => array:1 [ …1] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin: From a small molecule to brain functions" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neubiorev.2020.03.012" "Revista" => array:6 [ "tituloSerie" => "Neurosci Biobehav Rev." "fecha" => "2020" "volumen" => "113" "paginaInicial" => "190" "paginaFinal" => "203" "link" => array:1 [ …1] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Crosstalk: The diversity of melanopsin ganglion cell types has begun to challenge the canonical divide between image‐forming and non‐image‐forming vision" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.24873" "Revista" => array:2 [ "tituloSerie" => "J Comp Neurol." "fecha" => "2020" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term effect of optic nerve axotomy on the retinal ganglion cell layer" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1167/iovs.15-17195" "Revista" => array:5 [ "tituloSerie" => "Investig Ophthalmol Vis Sci." "fecha" => "2015" "volumen" => "56" "paginaInicial" => "6095" "paginaFinal" => "6112" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The functional diversity of retinal ganglion cells in the mouse" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature16468" "Revista" => array:6 [ "tituloSerie" => "Nature." "fecha" => "2016" "volumen" => "529" "paginaInicial" => "345" "paginaFinal" => "350" "link" => array:1 [ …1] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Parallel processing in the mammalian retina" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrn1497" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Neurosci." "fecha" => "2004" "volumen" => "5" "paginaInicial" => "747" "paginaFinal" => "757" "link" => array:1 [ …1] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Retinofugal projections in the mouse" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.23635" "Revista" => array:6 [ "tituloSerie" => "J Comp Neurol." "fecha" => "2014" "volumen" => "522" "paginaInicial" => "3733" "paginaFinal" => "3753" "link" => array:1 [ …1] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.1067262" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "2002" "volumen" => "295" "paginaInicial" => "1070" "paginaFinal" => "1073" "link" => array:1 [ …1] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.1069609" "Revista" => array:7 [ "tituloSerie" => "Science" "fecha" => "2002" "volumen" => "295" "paginaInicial" => "1065" "paginaFinal" => "1070" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin: An opsin in melanophores, brain, and eye" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.95.1.340" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci." "fecha" => "1998" "volumen" => "95" "paginaInicial" => "340" "paginaFinal" => "345" "link" => array:1 [ …1] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A Novel Human Opsin in the Inner Retina" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.20-02-00600.2000" "Revista" => array:7 [ "tituloSerie" => "J Neurosci." "fecha" => "2000" "volumen" => "20" "paginaInicial" => "600" "paginaFinal" => "605" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin Is Expressed in PACAP-Containing Retinal Ganglion Cells of the Human Retinohypothalamic Tract" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1167/iovs.04-0313" "Revista" => array:5 [ "tituloSerie" => "Investig Opthalmology Vis Sci." "fecha" => "2004" "volumen" => "45" "paginaInicial" => "4202" "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature03387" "Revista" => array:6 [ "tituloSerie" => "Nature." "fecha" => "2005" "volumen" => "433" "paginaInicial" => "749" "paginaFinal" => "754" "link" => array:1 [ …1] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PACAP and glutamate are co-stored in the retinohypothalamic tract" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Comp Neurol." "fecha" => "2000" "volumen" => "418" "paginaInicial" => "147" "paginaFinal" => "155" "link" => array:1 [ …1] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.1077293" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "2003" "volumen" => "299" "paginaInicial" => "245" "paginaFinal" => "247" "link" => array:1 [ …1] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin and rod–cone photoreceptive systems account for all major accessory visual functions in mice" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature01761" "Revista" => array:5 [ "tituloSerie" => "Nature." "fecha" => "2003" "volumen" => "424" "paginaInicial" => "75" "paginaFinal" => "81" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature06829" "Revista" => array:6 [ "tituloSerie" => "Nature." "fecha" => "2008" "volumen" => "453" "paginaInicial" => "102" "paginaFinal" => "105" "link" => array:1 [ …1] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inducible Ablation of Melanopsin-Expressing Retinal Ganglion Cells Reveals Their Central Role in Non-Image Forming Visual Responses" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0002451" "Revista" => array:5 [ "tituloSerie" => "PLoS One." "fecha" => "2008" "volumen" => "3" "paginaInicial" => "e2451" "link" => array:1 [ …1] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Photopigment Melanopsin Is Exclusively Present in Pituitary Adenylate Cyclase-Activating Polypeptide-Containing Retinal Ganglion Cells of the Retinohypothalamic Tract" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.22-01-j0002.2002" "Revista" => array:6 [ "tituloSerie" => "J Neurosci." "fecha" => "2002" "volumen" => "22" "paginaInicial" => "RC191" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin Contributions to Irradiance Coding in the Thalamo-Cortical Visual System" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pbio.1000558" "Revista" => array:4 [ "tituloSerie" => "PLoS Biol." "fecha" => "2010" "volumen" => "8" "link" => array:1 [ …1] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-Expressing Retinal Ganglion-Cell Photoreceptors: Cellular Diversity and Role in Pattern Vision" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neuron.2010.05.023" "Revista" => array:6 [ "tituloSerie" => "Neuron." "fecha" => "2010" "volumen" => "67" "paginaInicial" => "49" "paginaFinal" => "60" "link" => array:1 [ …1] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Form and Function of the M4 Cell, an Intrinsically Photosensitive Retinal Ganglion Cell Type Contributing to Geniculocortical Vision" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.1422-12.2012" "Revista" => array:6 [ "tituloSerie" => "J Neurosci." "fecha" => "2012" "volumen" => "32" "paginaInicial" => "13608" "paginaFinal" => "13620" "link" => array:1 [ …1] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A Role for Melanopsin in Alpha Retinal Ganglion Cells and Contrast Detection" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neuron.2014.03.022" "Revista" => array:6 [ "tituloSerie" => "Neuron." "fecha" => "2014" "volumen" => "82" "paginaInicial" => "781" "paginaFinal" => "788" "link" => array:1 [ …1] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The M5 Cell: A Color-Opponent Intrinsically Photosensitive Retinal Ganglion Cell" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neuron.2017.11.030" "Revista" => array:7 [ "tituloSerie" => "Neuron." "fecha" => "2018" "volumen" => "97" "paginaInicial" => "150" "paginaFinal" => "163" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The M6 cell: A small-field bistratified photosensitive retinal ganglion cell" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.24556" "Revista" => array:6 [ "tituloSerie" => "J Comp Neurol." "fecha" => "2019" "volumen" => "527" "paginaInicial" => "297" "paginaFinal" => "311" "link" => array:1 [ …1] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin Contributions to the Representation of Images in the Early Visual System" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cub.2017.04.046" "Revista" => array:6 [ "tituloSerie" => "Curr Biol." "fecha" => "2017" "volumen" => "27" "paginaInicial" => "1623" "paginaFinal" => "1632" "link" => array:1 [ …1] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Form vision from melanopsin in humans" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41467-019-10113-3" "Revista" => array:5 [ "tituloSerie" => "Nat Commun." "fecha" => "2019" "volumen" => "10" "paginaInicial" => "2274" "link" => array:1 [ …1] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Morphology and mosaics of melanopsin-expressing retinal ganglion cell types in mice" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.22381" "Revista" => array:4 [ "tituloSerie" => "J Comp Neurol." "fecha" => "2010" "volumen" => "518" "paginaInicial" => "NA" ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.tins.2011.07.001" "Revista" => array:6 [ "tituloSerie" => "Trends Neurosci." "fecha" => "2011" "volumen" => "34" "paginaInicial" => "572" "paginaFinal" => "580" "link" => array:1 [ …1] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mood, the Circadian System, and Melanopsin Retinal Ganglion Cells" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev-neuro-072116-031324" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Neurosci." "fecha" => "2017" "volumen" => "40" "paginaInicial" => "539" "paginaFinal" => "556" "link" => array:1 [ …1] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transcriptomic Signatures of Postnatal and Adult Intrinsically Photosensitive Ganglion Cells" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/ENEURO.0022-19.2019" "Revista" => array:4 [ "tituloSerie" => "Eneuro." "fecha" => "2019" "volumen" => "6" "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.22579" "Revista" => array:6 [ "tituloSerie" => "J Comp Neurol." …5 ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Displaced retinal ganglion cells in albino and pigmented rats" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fnana.2014.00099" "Revista" => array:5 [ …5] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Retinal neurodegeneration in experimental glaucoma" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/bs.pbr.2015.04.008" "Revista" => array:6 [ …6] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identifying specific RGC types may shed light on their idiosyncratic responses to neuroprotection" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/1673-5374.162751" "Revista" => array:2 [ …2] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular Hypertension" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fnins.2017.00235" "Revista" => array:5 [ …5] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin expression is an indicator of the well-being of melanopsin-expressing retinal ganglion cells but not of their viability" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/1673-5374.189182" "Revista" => array:5 [ …5] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nerve fibre layer degeneration and retinal ganglion cell loss long term after optic nerve crush or transection in adult mice" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.exer.2018.02.010" "Revista" => array:6 [ …6] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of Ocular Hypertension in the Visual System of Pigmented Mice" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0121134" "Revista" => array:5 [ …5] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "BDNF rescues RGCs but not intrinsically photosensitive RGCs in ocular hypertensive albino rat retinas" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1167/iovs.15-16454" "Revista" => array:5 [ …5] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/ijms20123012" "Revista" => array:4 [ …4] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn3a" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1167/iovs.15-16808" "Revista" => array:4 [ …4] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0255" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Light-induced retinal degeneration causes a transient downregulation of melanopsin in the rat retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.exer.2017.05.010" "Revista" => array:6 [ …6] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0260" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-containing or non-melanopsin-containing retinal ganglion cells response to acute ocular hypertension with or without brain-derived neurotrophic factor neuroprotection" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1167/iovs.16-20146" "Revista" => array:5 [ …5] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0265" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Whole Number, Distribution and Co-Expression of Brn3 Transcription Factors in Retinal Ganglion Cells of Adult Albino and Pigmented Rats" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0049830" "Revista" => array:4 [ …4] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0270" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Number and spatial distribution of intrinsically photosensitive retinal ganglion cells in the adult albino rat" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.exer.2012.12.010" "Revista" => array:6 [ …6] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0275" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature10206" "Revista" => array:6 [ …6] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0280" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7554/eLife.22861" "Revista" => array:4 [ …4] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0285" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Distribution of melanopsin positive neurons in pigmented and albino mice: evidence for melanopsin interneurons in the mouse retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fnana.2014.00131" "Revista" => array:5 [ …5] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0290" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Light and Darkness Regulate Melanopsin in the Retinal Ganglion Cells of the Albino Wistar Rat" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1385/JMN:27:2:147" "Revista" => array:6 [ …6] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0295" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin changes in neonatal albino rat independent of rods and cones" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/WNR.0b013e328010ff56" "Revista" => array:6 [ …6] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0300" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differential expression of melanopsin mRNA and protein in Brown Norwegian rats" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.exer.2012.11.006" "Revista" => array:6 [ …6] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0305" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differential Expression of Two Distinct Functional Isoforms of Melanopsin (Opn4) in the Mammalian Retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.2036-09.2009" "Revista" => array:6 [ …6] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0310" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin expressing human retinal ganglion cells: Subtypes, distribution, and intraretinal connectivity" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.24181" "Revista" => array:6 [ …6] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0315" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin Phototransduction Is Repurposed by ipRGC Subtypes to Shape the Function of Distinct Visual Circuits" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neuron.2018.06.032" "Revista" => array:6 [ …6] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0320" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Subtype-Specific Regeneration of Retinal Ganglion Cells following Axotomy: Effects of Osteopontin and mTOR Signaling" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neuron.2015.02.017" "Revista" => array:6 [ …6] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0325" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Light as a central modulator of circadian rhythms, sleep and affect" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrn3743" "Revista" => array:6 [ …6] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0330" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Retinofugal Projections from Melanopsin-Expressing Retinal Ganglion Cells Revealed by Intraocular Injections of Cre-Dependent Virus" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0149501" "Revista" => array:4 [ …4] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0335" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A Broad Role for Melanopsin in Nonvisual Photoreception" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.23-18-07093.2003" "Revista" => array:6 [ …6] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0340" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Divergent projection patterns of M1 ipRGC subtypes" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.24469" "Revista" => array:6 [ …6] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0345" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin and the Intrinsically Photosensitive Retinal Ganglion Cells: Biophysics to Behavior" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neuron.2019.07.016" "Revista" => array:6 [ …6] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0350" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Can We See with Melanopsin?" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ …3] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0355" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin ganglion cell outer retinal dendrites: Morphologically distinct and asymmetrically distributed in the mouse retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.24293" "Revista" => array:6 [ …6] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0360" "etiqueta" => "72" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.celrep.2018.04.086" "Revista" => array:7 [ …7] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0365" "etiqueta" => "73" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent axon collaterals of intrinsically photosensitive retinal ganglion cells" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1017/S0952523813000199" "Revista" => array:6 [ …6] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0370" "etiqueta" => "74" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "M1 ipRGCs Influence Visual Function through Retrograde Signaling in the Retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.3500-15.2016" "Revista" => array:6 [ …6] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0375" "etiqueta" => "75" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Architecture of retinal projections to the central circadian pacemaker" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.1523629113" "Revista" => array:6 [ …6] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib0380" "etiqueta" => "76" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1113/jphysiol.2013.262782" "Revista" => array:6 [ …6] ] ] ] ] ] 76 => array:3 [ "identificador" => "bib0385" "etiqueta" => "77" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Overlapping morphological and functional properties between M4 and M5 intrinsically photosensitive retinal ganglion cells" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.24806" "Revista" => array:6 [ …6] ] ] ] ] ] 77 => array:3 [ "identificador" => "bib0390" "etiqueta" => "78" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Roles of Rods, Cones, and Melanopsin in Photoresponses of M4 Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) and Optokinetic Visual Behavior" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fncel.2018.00203" "Revista" => array:5 [ …5] ] ] ] ] ] 78 => array:3 [ "identificador" => "bib0395" "etiqueta" => "79" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Four alpha ganglion cell types in mouse retina: Function, structure, and molecular signatures" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0180091" "Revista" => array:4 [ …4] ] ] ] ] ] 79 => array:3 [ "identificador" => "bib0400" "etiqueta" => "80" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Colour As a Signal for Entraining the Mammalian Circadian Clock" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pbio.1002127" "Revista" => array:3 [ …3] ] ] ] ] ] 80 => array:3 [ "identificador" => "bib0405" "etiqueta" => "81" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-expressing ganglion cells on macaque and human retinas form two morphologically distinct populations" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.23995" "Revista" => array:6 [ …6] ] ] ] ] ] 81 => array:3 [ "identificador" => "bib0410" "etiqueta" => "82" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-expressing retinal ganglion cells in aging and disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.14670/HH-18-138" "Revista" => array:6 [ …6] ] ] ] ] ] 82 => array:3 [ "identificador" => "bib0415" "etiqueta" => "83" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/brain/awq155" "Revista" => array:6 [ …6] ] ] ] ] ] 83 => array:3 [ "identificador" => "bib0420" "etiqueta" => "84" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Photosensitive melanopsin-containing retinal ganglion cells in health and disease: implications for circadian rhythms" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/ijms20133164" "Revista" => array:4 [ …4] ] ] ] ] ] 84 => array:3 [ "identificador" => "bib0425" "etiqueta" => "85" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A color vision circuit for non-image-forming vision in the primate retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cub.2020.01.040" "Revista" => array:6 [ …6] ] ] ] ] ] 85 => array:3 [ "identificador" => "bib0430" "etiqueta" => "86" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cne.23588" "Revista" => array:5 [ …5] ] ] ] ] ] 86 => array:3 [ "identificador" => "bib0435" "etiqueta" => "87" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0003153" "Revista" => array:5 [ …5] ] ] ] ] ] 87 => array:3 [ "identificador" => "bib0440" "etiqueta" => "88" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical implications of the melanopsin-based non–image-forming visual system" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1212/WNL.0000000000003761" "Revista" => array:7 [ …7] ] ] ] ] ] 88 => array:3 [ "identificador" => "bib0445" "etiqueta" => "89" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypomorphic Expression of Pitx3 Disrupts Circadian Clocks and Prevents Metabolic Entrainment of Energy Expenditure" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.celrep.2019.11.027" "Revista" => array:6 [ …6] ] ] ] ] ] 89 => array:3 [ "identificador" => "bib0450" "etiqueta" => "90" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Local photic entrainment of the retinal circadian oscillator in the absence of rods, cones, and melanopsin" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.1323350111" "Revista" => array:7 [ …7] ] ] ] ] ] 90 => array:3 [ "identificador" => "bib0455" "etiqueta" => "91" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The post-illumination pupil response is reduced in glaucoma patients" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1167/iovs.10-6023" "Revista" => array:4 [ …4] ] ] ] ] ] 91 => array:3 [ "identificador" => "bib0460" "etiqueta" => "92" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Measuring and using light in the melanopsin age" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.tins.2013.10.004" "Revista" => array:6 [ …6] ] ] ] ] ] 92 => array:3 [ "identificador" => "bib0465" "etiqueta" => "93" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Binocular summation in postillumination pupil response driven by melanopsin-containing retinal ganglion cells" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1167/iovs.18-24639" "Revista" => array:4 [ …4] ] ] ] ] ] 93 => array:3 [ "identificador" => "bib0470" "etiqueta" => "94" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Additive contributions of melanopsin and both cone types provide broadband sensitivity to mouse pupil control" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12915-018-0552-1" "Revista" => array:5 [ …5] ] ] ] ] ] 94 => array:3 [ "identificador" => "bib0475" "etiqueta" => "95" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The acute light-induction of sleep is mediated by OPN4-based photoreception" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nn.2179" "Revista" => array:6 [ …6] ] ] ] ] ] 95 => array:3 [ "identificador" => "bib0480" "etiqueta" => "96" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Type I intrinsically photosensitive retinal ganglion cells of early post-natal development correspond to the M4 subtype" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13064-015-0042-x" "Revista" => array:5 [ …5] ] ] ] ] ] 96 => array:3 [ "identificador" => "bib0485" "etiqueta" => "97" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dissecting a Role for Melanopsin in Behavioural Light Aversion Reveals a Response Independent of Conventional Photoreception" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0015009" "Revista" => array:4 [ …4] ] ] ] ] ] 97 => array:3 [ "identificador" => "bib0490" "etiqueta" => "98" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-dependent light avoidance in neonatal mice" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.1008533107" "Revista" => array:7 [ …7] ] ] ] ] ] 98 => array:3 [ "identificador" => "bib0495" "etiqueta" => "99" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Response of the infant rat to light prior to eyelid opening: Mediation by the superior colliculus" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/dev.420110510" "Revista" => array:6 [ …6] ] ] ] ] ] 99 => array:3 [ "identificador" => "bib0500" "etiqueta" => "100" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development of melanopsin-based irradiance detecting circuitry" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1749-8104-6-8" "Revista" => array:5 [ …5] ] ] ] ] ] 100 => array:3 [ "identificador" => "bib0505" "etiqueta" => "101" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cub.2007.04.058" "Revista" => array:6 [ …6] ] ] ] ] ] 101 => array:3 [ "identificador" => "bib0510" "etiqueta" => "102" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Retinal dopamine mediates multiple dimensions of light-adapted vision" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.0711-12.2012" "Revista" => array:7 [ …7] ] ] ] ] ] 102 => array:3 [ "identificador" => "bib0515" "etiqueta" => "103" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Behavioral assessment of visual acuity in mice and rats" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0042-6989(00)00081-X" "Revista" => array:6 [ …6] ] ] ] ] ] 103 => array:3 [ "identificador" => "bib0520" "etiqueta" => "104" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-driven increases in maintained activity enhance thalamic visual response reliability across a simulated dawn" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.1505274112" "Revista" => array:6 [ …6] ] ] ] ] ] 104 => array:3 [ "identificador" => "bib0525" "etiqueta" => "105" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A Colourful Clock" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pbio.1002160" "Revista" => array:3 [ …3] ] ] ] ] ] 105 => array:3 [ "identificador" => "bib0530" "etiqueta" => "106" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chromatic clocks: Color opponency in non-image-forming visual function" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neubiorev.2017.04.016" "Revista" => array:7 [ …7] ] ] ] ] ] 106 => array:3 [ "identificador" => "bib0535" "etiqueta" => "107" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Degeneration of human photosensitive retinal ganglion cells may explain sleep and circadian rhythms disorders in Parkinson’s disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40478-018-0596-z" "Revista" => array:6 [ …6] ] ] ] ] ] 107 => array:3 [ "identificador" => "bib0540" "etiqueta" => "108" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Loss of melanopsin-expressing ganglion cell subtypes and dendritic degeneration in the aging human retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fnagi.2017.00079" "Revista" => array:5 [ …5] ] ] ] ] ] 108 => array:3 [ "identificador" => "bib0545" "etiqueta" => "109" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin retinal ganglion cell loss in Alzheimer disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ana.24548" "Revista" => array:6 [ …6] ] ] ] ] ] 109 => array:3 [ "identificador" => "bib0550" "etiqueta" => "110" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ophtha.2018.01.036" "Revista" => array:6 [ …6] ] ] ] ] ] 110 => array:3 [ "identificador" => "bib0555" "etiqueta" => "111" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Circadian Rhythm Disorders and Melatonin Production in 127 Blind Women with and without Light Perception" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0748730414536852" "Revista" => array:7 [ …7] ] ] ] ] ] 111 => array:3 [ "identificador" => "bib0560" "etiqueta" => "112" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Physiologic Diversity and Development of Intrinsically Photosensitive Retinal Ganglion Cells" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neuron.2005.09.031" "Revista" => array:6 [ …6] ] ] ] ] ] 112 => array:3 [ "identificador" => "bib0565" "etiqueta" => "113" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cellular properties of intrinsically photosensitive retinal ganglion cells during postnatal development" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13064-019-0132-2" "Revista" => array:5 [ …5] ] ] ] ] ] 113 => array:3 [ "identificador" => "bib0570" "etiqueta" => "114" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin-Dependent Photoreception Provides Earliest Light Detection in the Mammalian Retina" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cub.2005.05.053" "Revista" => array:6 [ …6] ] ] ] ] ] 114 => array:3 [ "identificador" => "bib0575" "etiqueta" => "115" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A direct and melanopsin-dependent fetal light response regulates mouse eye development" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature11823" "Revista" => array:6 [ …6] ] ] ] ] ] 115 => array:3 [ "identificador" => "bib0580" "etiqueta" => "116" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intrinsically photosensitive ganglion cells contribute to plasticity in retinal wave circuits" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.1222150110" "Revista" => array:6 [ …6] ] ] ] ] ] 116 => array:3 [ "identificador" => "bib0585" "etiqueta" => "117" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Light acts through melanopsin to alter retinal waves and segregation of retinogeniculate afferents" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nn.2845" "Revista" => array:7 [ …7] ] ] ] ] ] 117 => array:3 [ "identificador" => "bib0590" "etiqueta" => "118" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin ganglion cells use a membrane-associated rhabdomeric phototransduction cascade" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/jn.01066.2007" "Revista" => array:6 [ …6] ] ] ] ] ] 118 => array:3 [ "identificador" => "bib0595" "etiqueta" => "119" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterisation of light responses in the retina of mice lacking principle components of rod, cone and melanopsin phototransduction signalling pathways" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/srep28086" "Revista" => array:5 [ …5] ] ] ] ] ] 119 => array:3 [ "identificador" => "bib0600" "etiqueta" => "120" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanopsin phototransduction: great excitement over a poor catch" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cub.2009.01.034" "Revista" => array:6 [ …6] ] ] ] ] ] 120 => array:3 [ "identificador" => "bib0605" "etiqueta" => "121" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "M1 intrinsically photosensitive retinal ganglion cells integrate rod and melanopsin inputs to signal in low light" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.celrep.2019.11.024" "Revista" => array:6 [ …6] ] ] ] ] ] 121 => array:3 [ "identificador" => "bib0610" "etiqueta" => "122" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A retinal ganglion cell that can signal irradiance continuously for 10 hours" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.1423-12.2012" "Revista" => array:6 [ …6] ] ] ] ] ] 122 => array:3 [ "identificador" => "bib0615" "etiqueta" => "123" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chromophore regeneration: Melanopsin does its own thing" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.0603955103" "Revista" => array:6 [ …6] ] ] ] ] ] 123 => array:3 [ "identificador" => "bib0620" "etiqueta" => "124" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Structural basis for ON-and OFF-center responses in retinal ganglion cells" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.959847" "Revista" => array:6 [ …6] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735794/0000009600000006/v1_202106040601/S2173579420302401/v1_202106040601/en/main.assets" "Apartado" => array:4 [ "identificador" => "5815" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735794/0000009600000006/v1_202106040601/S2173579420302401/v1_202106040601/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420302401?idApp=UINPBA00004N"]

Statistics

Review

Photosensitive ganglion cells: A diminutive, yet essential population

Células ganglionares fotosensibles: una población diminuta pero esencial

B. Vidal-Villegasa,

Corresponding author

beatrizvidalvillegas@gmail.com

Corresponding author.

, A. Gallego-Ortegab, J.A. Miralles de Imperial-Ollerob, J.M. Martínez de la Casaa, J. García Feijooa, M. Vidal-Sanzb

a Servicio de Oftalmología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain

b Departamento de Oftalmología, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria (IMIB) Virgen de la Arrixaca. El Palmar, Murcia, Spain

Read

Times
was read the article

Total PDF

Total HTML

Share statistics

 array:24 [
  "pii" => "S2173579420302401"
  "issn" => "21735794"
  "doi" => "10.1016/j.oftale.2020.06.020"
  "estado" => "S300"
  "fechaPublicacion" => "2021-06-01"
  "aid" => "1813"
  "copyright" => "Sociedad Espa&#241;ola de Oftalmolog&#237;a"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "rev"
  "cita" => "Arch Soc Esp Oftalmol. 2021;96:299-315"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0365669120303476"
      "issn" => "03656691"
      "doi" => "10.1016/j.oftal.2020.06.032"
      "estado" => "S300"
      "fechaPublicacion" => "2021-06-01"
      "aid" => "1813"
      "copyright" => "Sociedad Espa&#241;ola de Oftalmolog&#237;a"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "rev"
      "cita" => "Arch Soc Esp Oftalmol. 2021;96:299-315"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:1 [
        "total" => 0
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Revisi&#243;n</span>"
        "titulo" => "C&#233;lulas ganglionares fotosensibles&#58; una poblaci&#243;n diminuta pero esencial"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "299"
            "paginaFinal" => "315"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Photosensitive ganglion cells&#58; A diminutive&#44; yet essential population"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 1479
                "Ancho" => 1740
                "Tamanyo" => 691252
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A&#41; Fotomontaje de una retina de rata adulta en la que se aprecian c&#233;lulas ganglionares de la retina intr&#237;nsecamente fotosensibles &#40;CGRif&#41; marcadas con melanopsina &#40;CGRm<span class="elsevierStyleSup">&#43;</span>&#41;&#44; distribuidas por toda la retina&#46; B&#41; Mapa de vecinos de la misma retina &#40;A&#41; que muestra la distribuci&#243;n topogr&#225;fica de las CGRm<span class="elsevierStyleSup">&#43;</span>&#44; que se contabilizaron manualmente&#44; un total de 2&#46;683&#46; Escala de color del mapa de vecinos en la que cada color representa un incremento de 4 vecinos en un radio de 0&#44;22<span class="elsevierStyleHsp" style=""></span>mm y oscila desde p&#250;rpura &#40;0-6 vecinos&#41; a rojo oscuro &#40;42-48 vecinos&#41;&#46; C y D&#41; Detalles a mayor aumento en los que se aprecia el marcaje de las CGRif&#44; tanto en sus somas celulares como en sus extensas dendritas en el plano de foco&#46;</p> <p id="spar0014" class="elsevierStyleSimplePara elsevierViewall">Barra&#58; A&#58;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#61;</span><span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm&#44; C&#58;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>&#956;m&#44; D<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25<span class="elsevierStyleHsp" style=""></span>&#956;m&#59; I&#58; inferior&#59; N&#58; nasal&#59; S&#58; superior&#59; T&#58; temporal&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "B&#46; Vidal-Villegas, A&#46; Gallego-Ortega, J&#46;A&#46; Miralles de Imperial-Ollero, J&#46;M&#46; Mart&#237;nez de la Casa, J&#46; Garc&#237;a Feijoo, M&#46; Vidal-Sanz"
            "autores" => array:6 [
              0 => array:2 [
                "nombre" => "B&#46;"
                "apellidos" => "Vidal-Villegas"
              ]
              1 => array:2 [
                "nombre" => "A&#46;"
                "apellidos" => "Gallego-Ortega"
              ]
              2 => array:2 [
                "nombre" => "J&#46;A&#46;"
                "apellidos" => "Miralles de Imperial-Ollero"
              ]
              3 => array:2 [
                "nombre" => "J&#46;M&#46;"
                "apellidos" => "Mart&#237;nez de la Casa"
              ]
              4 => array:2 [
                "nombre" => "J&#46;"
                "apellidos" => "Garc&#237;a Feijoo"
              ]
              5 => array:2 [
                "nombre" => "M&#46;"
                "apellidos" => "Vidal-Sanz"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2173579420302401"
          "doi" => "10.1016/j.oftale.2020.06.020"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420302401?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669120303476?idApp=UINPBA00004N"
      "url" => "/03656691/0000009600000006/v1_202106010616/S0365669120303476/v1_202106010616/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2173579420302486"
    "issn" => "21735794"
    "doi" => "10.1016/j.oftale.2020.06.025"
    "estado" => "S300"
    "fechaPublicacion" => "2021-06-01"
    "aid" => "1811"
    "copyright" => "Sociedad Espa&#241;ola de Oftalmolog&#237;a"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Arch Soc Esp Oftalmol. 2021;96:316-20"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Short communication</span>"
      "titulo" => "Visual impairment induced by prosthetic cobaltism"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "316"
          "paginaFinal" => "320"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Afectaci&#243;n visual por cobaltismo prot&#233;sico"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0010"
          "etiqueta" => "Figure 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1096
              "Ancho" => 1255
              "Tamanyo" => 226062
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0010"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A&#46; Fundus within normal range&#46; B&#46; Computerized campimetry showing visual field retraction in both eyes&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "B&#46;F&#46; S&#225;nchez-Dalmau, F&#46; Spencer, L&#46; S&#225;nchez-Vela, A&#46; Cam&#243;s-Carreras, S&#46; Nogu&#233; Xarau, J&#46;A&#46; Fern&#225;ndez-Valencia"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "B&#46;F&#46;"
              "apellidos" => "S&#225;nchez-Dalmau"
            ]
            1 => array:2 [
              "nombre" => "F&#46;"
              "apellidos" => "Spencer"
            ]
            2 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "S&#225;nchez-Vela"
            ]
            3 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Cam&#243;s-Carreras"
            ]
            4 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Nogu&#233; Xarau"
            ]
            5 => array:2 [
              "nombre" => "J&#46;A&#46;"
              "apellidos" => "Fern&#225;ndez-Valencia"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0365669120303452"
        "doi" => "10.1016/j.oftal.2020.06.030"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669120303452?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420302486?idApp=UINPBA00004N"
    "url" => "/21735794/0000009600000006/v1_202106040601/S2173579420302486/v1_202106040601/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2173579420302528"
    "issn" => "21735794"
    "doi" => "10.1016/j.oftale.2020.09.004"
    "estado" => "S300"
    "fechaPublicacion" => "2021-06-01"
    "aid" => "1824"
    "copyright" => "Sociedad Espa&#241;ola de Oftalmolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Arch Soc Esp Oftalmol. 2021;96:293-8"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Management of strabismus related to infantile glaucoma&#58; Case series"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "293"
          "paginaFinal" => "298"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Manejo del estrabismo asociado al glaucoma de la infancia&#58; serie de casos"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 355
              "Ancho" => 900
              "Tamanyo" => 35770
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0005"
              "detalle" => "Fig&#46; "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient number 5&#46; Exotropia in patient with glaucoma secondary to trauma in left eye&#44; with low visual acuity and multiple glaucoma surgeries in that eye&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "N&#46; G&#252;emes Villahoz, L&#46; Morales Fern&#225;ndez, C&#46; Narv&#225;ez Palaz&#243;n, M&#46;N&#46; Moreno, M&#46;R&#46; G&#243;mez de Lia&#241;o S&#225;nchez"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "N&#46;"
              "apellidos" => "G&#252;emes Villahoz"
            ]
            1 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Morales Fern&#225;ndez"
            ]
            2 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "Narv&#225;ez Palaz&#243;n"
            ]
            3 => array:2 [
              "nombre" => "M&#46;N&#46;"
              "apellidos" => "Moreno"
            ]
            4 => array:2 [
              "nombre" => "M&#46;R&#46;"
              "apellidos" => "G&#243;mez de Lia&#241;o S&#225;nchez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0365669120303592"
        "doi" => "10.1016/j.oftal.2020.09.003"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669120303592?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420302528?idApp=UINPBA00004N"
    "url" => "/21735794/0000009600000006/v1_202106040601/S2173579420302528/v1_202106040601/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Photosensitive ganglion cells&#58; A diminutive&#44; yet essential population"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "299"
        "paginaFinal" => "315"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "B&#46; Vidal-Villegas, A&#46; Gallego-Ortega, J&#46;A&#46; Miralles de Imperial-Ollero, J&#46;M&#46; Mart&#237;nez de la Casa, J&#46; Garc&#237;a Feijoo, M&#46; Vidal-Sanz"
        "autores" => array:6 [
          0 => array:4 [
            "nombre" => "B&#46;"
            "apellidos" => "Vidal-Villegas"
            "email" => array:1 [
              0 => "beatrizvidalvillegas@gmail.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "A&#46;"
            "apellidos" => "Gallego-Ortega"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "J&#46;A&#46;"
            "apellidos" => "Miralles de Imperial-Ollero"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "J&#46;M&#46;"
            "apellidos" => "Mart&#237;nez de la Casa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "J&#46;"
            "apellidos" => "Garc&#237;a Feijoo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "M&#46;"
            "apellidos" => "Vidal-Sanz"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Servicio de Oftalmolog&#237;a&#44; Hospital Cl&#237;nico San Carlos&#44; Instituto de Investigaci&#243;n Sanitaria del Hospital Cl&#237;nico San Carlos &#40;IdISSC&#41;&#44; Madrid&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Departamento de Oftalmolog&#237;a&#44; Universidad de Murcia e Instituto Murciano de Investigaci&#243;n Biosanitaria &#40;IMIB&#41; Virgen de la Arrixaca&#46; El Palmar&#44; Murcia&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "C&#233;lulas ganglionares fotosensibles&#58; una poblaci&#243;n diminuta pero esencial"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2487
            "Ancho" => 2925
            "Tamanyo" => 1377491
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A&#41; Photomontage of an adult rat retina showing intrinsically photosensitive retinal ganglion cells &#40;RGCif&#41; marked with melanopsin &#40;RGCm<span class="elsevierStyleSup">&#43;</span>&#41;&#44; distributed throughout the retina&#46; B&#41; Adjacency map of the same retina &#40;A&#41; that shows the topographic distribution of the RGCm<span class="elsevierStyleSup">&#43;</span>&#44; which were counted manually&#44; a total of 2&#44;683&#46; Colour scale of the adjacency map in which each colour represents an increase of 4 adjacents within a radius of 0&#46;22<span class="elsevierStyleHsp" style=""></span>mm and ranges from purple &#40;0-6 adjacents&#41; to dark red &#40;42-48 adjacents&#41;&#46; C and D&#41; Details with a greater increase in which the marking of the RGCif can be seen&#44; both in their cellular somas and in their extensive dendrites in the focus plane &#40;For interpretation of the references to colour in this figure legend&#44; the reader is referred to the web version of this article&#41;&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Bar&#58; A&#58;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm&#44; C&#58;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>&#956; m&#44; D<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25<span class="elsevierStyleHsp" style=""></span>&#956; m&#59; I&#58; lower&#59; N&#58; nasal&#59; S&#58; upper&#59; T&#58; temporary&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">The retina</span><p id="par0005" class="elsevierStylePara elsevierViewall">One of the main functions of the retina&#44; that of obtaining light information from our environment&#44; is carried out by photoreceptors&#44; neurons full of visual pigments and specialised for phototransduction&#44; i&#46;e&#46; capturing electromagnetic energy &#40;wavelengths within the visible spectrum&#41; and converting it into electrical energy&#46; The capture of a photon by the visual pigments induces a change in the molecule that activates a G-protein which&#44; in turn&#44; sets in motion an intracellular cascade that ends in a transitory change in the membrane potential of the photoreceptor&#44; a hyperpolarisation&#44; a signal that serves as an interneuronal communication and is transmitted to other neurons in the retina for further processing&#46; In addition&#44; the retina has the function of comparing light signals detected by the photoreceptors and producing response patterns that can range from basic information about the level of environmental illumination to the image pattern detected by a single photoreceptor in the foveal region&#59; a region of the retina specialised for our fine vision that determines our spatial and temporal visual acuity as well as our ability to see colours&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The retina is capable of performing these functions by adapting to illumination intensities in the range of 10 logarithmic units and&#44; despite changing ambient light intensity&#44; maintains the same appearance of the objects we see&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Imaging and non-imaging paths</span><p id="par0010" class="elsevierStylePara elsevierViewall">The information sent by the retina is responsible on the one hand for the formation of images &#40;FI&#41; for our conscious visual perception of the world around us and&#44; on the other hand&#44; for non-image-forming visual functions &#40;NFI&#41; which nevertheless have important implications for our physiology and daily behaviour&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The vast majority of our retinal ganglion cells &#40;RGC&#41; work for the FI of our visual environment&#44; i&#46;e&#46; our conscious visual perception&#44; the location and perception of shapes&#44; their texture&#44; colour&#44; movement and perspective&#46; In humans and primates&#44; approximately 90&#37; of RGCs go to the geniculated nucleus of the thalamus&#44; the most important central relay station of visual information before they go to the striated visual cortex&#44; the first working station in the arduous elaboration of our conscious visual perception&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Another group of slightly less than 10&#37; of RGCs are dedicated to reflex maintenance tasks&#44; of which we are not aware but which also contribute to FI and are fundamental to our vision&#44; such as eye movements when faced with a new visual scene or the stabilisation of a moving visual scene&#44; or to accommodate and converge in front of nearby objects or to focus on distant objects&#46; All the nuclei that participate in FI generally have a topographic representation of the surface of the retina or retinotopic map&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Finally&#44; in humans and primates there is a very small percentage of RGCs that express the melanopsin photopigment and use the intensity of environmental light &#40;irradiance&#41; to regulate behavioural and physiological functions the circuits of which do not form images and have no relation to the conscious perception of vision&#46; These functions are collectively referred to as the NFI visual functions&#46; They enable the body to set the time of our central circadian clock and to anticipate changes in the environment by modifying its behaviour&#44; and to regulate the photomotor reflex&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Many additional behaviours also depend on the level of environmental lighting&#44; such as regulation of metabolic homeostasis&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> melatonin synthesis&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> our mood and cognitive abilities&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> body temperature&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> induction of sleep and alertness&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> masking of motor activity <span class="elsevierStyleItalic">and</span> aversion to light&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> or exacerbation of migraine and photophobia&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Although the knowledge we have today about our FI functions comes mostly from studies conducted in the visual system of primates and humans&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> most of the knowledge we have today about the NFI visual functions comes from studies conducted in rodents&#44; mainly in mice&#44; by the tools that have been made available for their identification and distinction from the other RGC&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;9&#8211;11</span></a> The use of techniques of genetic and molecular engineering has allowed the advance of our knowledge on the visual system of the mouse up to the point that it is at present the sensory system that is better known and surprisingly it is much more similar to that of the primate than we thought&#46; This paper reviews current concepts about the melanopathic pathway and its functions&#44; obtained from recent studies carried out mainly in mice&#46; We will also make a brief mention of the alterations of the melanopsynic pathway in some diseases&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Retinal ganglion cells</span><p id="par0035" class="elsevierStylePara elsevierViewall">The information processed in the retina is transmitted to the brain encoded in a train of nerve impulses by the RGC axons&#44; the only ones whose axons leave the retina and which account for a tiny proportion of retinal neurons&#46; For example&#44; in the adult rodent&#44; RGCs do not reach 1&#37; of the retinal neuron population&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Currently&#44; according to morphological&#44; physiological&#44; topographical&#44; molecular and innervation territory criteria&#44; it is thought that there are up to 40 different types of RGC&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Each one of these includes particular aspects of the visual scene that are transmitted in parallel to subcortical regions that perform specific tasks&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In the mouse&#44; up to 46 different subcortical targets have been described&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Inherently photosensitive retinal ganglion cells</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">General characteristics of intrinsically photosensitive retinal ganglion cells</span><p id="par0040" class="elsevierStylePara elsevierViewall">RGCs that are dedicated to NFI visual functions constitute a very small proportion &#40;in humans &#8776;1&#37; and in rodents &#8776;3&#37;&#44; see below&#41;&#46; These cells are characterised by the expression of the melanopsin pigment &#40;encoded by the Opn4 gene&#41;&#44; which transduces light into electrical signals&#44; hence they are called melanopsinic &#40;RGCm&#43;&#41;&#44; intrinsically photosensitive &#40;RGCif&#41;&#44; photosensitive or third retinal photoreceptor&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> Melanopsin takes its name from the melanophores in the skin of the frog where it was discovered&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> shortly after RGCifs were observed in monkeys and mice<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;19</span></a> and in the human retina&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> RGCifs in rodents and humans express 2 neurotransmitters&#44; glutamate and the polypeptide activator of pituitary adenylate cyclase &#40;PACAP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> RGCifs are depolarized in response to light stimulation of melanopsin&#44; even in the absence of information from cones and rods&#44; and also in vitro&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The elimination of melanopsin expression results in an attenuation of circadian synchronisation and photomotor reflex&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and the elimination of functional photoreception of the 3 photoreceptors &#40;rods&#44; cones and RGCif&#41;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> or genetic ablation of RGCifs<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a> causes the loss of visual NFI functions&#44; demonstrating that the origin of this melanopsynic pathway is in RGCif&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The first RGCifs described were the M1&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;19&#44;27</span></a> A few years later&#44; it was documented that RGCifs also projected into brain regions responsible for FI&#44; such as the superior colliculus &#40;SC&#41; &#40;quadrigeminal tuber in humans&#41; and the dorsal nucleus of the lateral geniculate &#40;dorsal geniculate nucleus in humans&#41;&#44; both in humans<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and in mice&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> In mice &#40;rd&#47;rd cl&#41;&#44; which do not have cones or rods but do have RGCif&#44; crude visual behaviour could be observed that resolved visual patterns and detected contrasts&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Later&#44; it was documented that most of the RGCif afferences to the dorsal division of the lateral geniculated nucleus &#40;LGNd&#41; came from the M4&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> which were soon identified as RGC &#945;-ON sustained with high contrast sensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> More recently&#44; 2 additional RGCifs with projection to the LGNd and possible contribution to spatial vision have been identified&#44; i&#46;e&#46;&#44; the M5&#44; which exhibits opposing colour responses<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> and the M6&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The contribution of RGCifs to spatial vision has been characterised in mice<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> and humans&#44; where they appear to contribute to the perception of brightness&#44; spatial vision and increased image appearance&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> At present&#44; six different types of RGCifs have been described in rodents&#44; which are called M1-M6 and are distinguished on the basis of their morphological characteristics&#44; size of their soma&#44; extension and stratification of their dendritic tree&#44; level of melanopsin expression&#44; intrinsic and extrinsic responses&#44; characteristics of their peripheral receptor fields&#44; regions of the brain to which they project and specific markers&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;28&#44;30&#44;32</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#44;36&#8211;40</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Number and distribution of intrinsically photosensitive retinal ganglion cells</span><p id="par0050" class="elsevierStylePara elsevierViewall">In adult rodents&#44; the Brn3a marker&#44; a Pou4f1 transcription factor&#44; can be used to identify the vast majority of conventional RGCs representing &#8776;96&#37; of RGCs&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> As the vast majority of Brn3a<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RGCs do not express melanopsin and viceversa&#44; the joint use of both markers allows to study in parallel but independently these 2 populations of RGCs under normal conditions and against different types of lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#8211;52</span></a> In rats&#44; the population of RGCif constitutes approximately 2&#46;5-2&#46;7&#37; of the total population of RGC in albino and pigmented retinas<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;27&#44;41&#8211;43&#44;49&#44;53&#44;54</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Similarly&#44; the use of Brn3b&#44; another Pou4f2 transcription factor&#44; and melanopsin as cellular markers makes it possible to identify a small subpopulation of RGCif M1 Brn3b- and distinguish it from the vast majority of M1s and all other M2-M6s which are Brn3b&#43;&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;56</span></a> In the pigmented mouse&#44; the total number of RGCifs has varied from 1&#44;02157 2&#44;05829 to 2&#44;57036&#46; These variations are due to the methodology used to identify RGCifs&#44; differences in the type of anti-melanopsin antibody&#44; immunohistochemical technique&#44; use or not of signal amplifiers or transgenic animals that express a marker in the melanopsin locus&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In rodents&#44; melanopsin expression is regulated by both light and retinal circadian rhythms<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">58&#8211;60</span></a> and in mice&#44; 2 isoforms of melanopsin has been described&#44; one long &#40;Opn4L&#41; and one short &#40;Opn4S&#41;&#44; which is expressed 40 times more than the long one&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">61&#44;62</span></a> M1 and M3 express both &#40;Opn4S and Opn4L&#41;&#44; while M2 and M4 only express Opn4L&#46; Of the different subtypes&#44; M1-M3 constitute the majority of RGCifs and are the easiest to identify as they express more melanopsin&#44; while M430&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> M5<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a> and M6<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> express melanopsin in very small quantities and are very difficult to identify with standard immunohistochemical techniques&#44; without amplification&#46; Currently&#44; it is accepted that RGCif constitute &#8776;3&#37; of mouse RGC&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;65</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The distribution of RGCifs differs&#59; almost all cellular subtypes &#40;except M3&#41; tessellate the retina&#44; M1 and M2 are more abundant in the upper hemirretin&#44; M5 are abundant in the lower hemirretin and M4 have a naso-temporal gradient with maximum densities in the super-temporal region&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">General projections of intrinsically photosensitive retinal ganglion cells</span><p id="par0065" class="elsevierStylePara elsevierViewall">RGCif projections have been studied in detail with techniques that increase the visibility of melanopsin or that use markers inserted in the melanopsin locus&#46; For example&#44; replacing the melanopsin gene with the sequence encoding tau-LacZ&#44; a protein composed of the enzyme&#946;galactosidase&#44; linked to a tau signal sequence &#40;an actin-associated protein that facilitates antegrade transport through the axon to the axonal terminal&#41; Opn4<span class="elsevierStyleSup">tauLacZ</span> &#40;Hattar<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44; 2002&#41;&#46; Immunohistochemical signal amplification techniques&#44; such as recombinant Cre29 or green fluorescent protein expression&#44; have also been used&#46; Axonal projections can be identified with the intravitreal injection of an adeno-associated virus &#40;AAV&#41; that transfects the human placental alkaline phosphatase gene &#40;AAV-fles-plap&#41; into transgenic mice expressing Cre under the melanopsin promoter &#40;Opn4<span class="elsevierStyleSup">Cre29&#44;66</span>&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Of the 46 subcortical territories that innervate the RGC&#44; 30&#37; lack innervation of the RGCif&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In general&#44; RGCifs project to the basal prosencephalon and hypothalamus&#44; the thalamus and habenula region&#44; the midbrain and the accessory optical system &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; In the basal prosencephalon they innervate the preoptic areas &#40;lateral&#44; medial and ventrolateral&#41;&#44; the perisupraoptic nucleus&#44; the subparaventricular zone &#40;sPVZ&#41;&#44; the suprachiasmatic nucleus &#40;SCN&#41;&#44; the anterior and lateral regions of the hypothalamus and the regions of the amygdala &#40;anterior&#44; medial and central&#41;&#44; as well as the nucleus of the terminal striae bed&#46; In the thalamus and the region of the habenula&#44; the perihabenular nucleus &#40;PHb&#41;&#44; the LGNd and the ventral lateral geniculated nucleus &#40;LGNv&#41;&#44; the intergeniculated leaflet and the <span class="elsevierStyleItalic">zona incerta</span> are innervated&#46; In the midbrain they innervate the pretectal olive nucleus &#40;PON&#41;&#44; the anterior&#44; medial and posterior pretectal nuclei&#44; and the nucleus of the optical tract&#46; In addition&#44; they innervate the visual layers of the SC&#44; the periaqueductal grey substance and the nuclei of the accessory optical system &#40;dorsal&#44; lateral and medial terminal nuclei&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;10&#44;11&#44;66&#8211;70</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">To summarise&#44; it could be said that most M1 and the rest of the RGCifs &#40;M2-M6&#41; are Brn3b&#43;&#44; projecting to the dorsal nucleus of the geniculate and SC&#44; are capable of mediating crude spatial vision in the absence of rod and cone function and of mediating contrast sensitivity &#40;M4&#41; or colour vision &#40;M5&#41;&#44; while the M1Brn3b- project exclusively to circadian centres&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Morphological characteristics and projections of intrinsically photosensitive retinal ganglion cells</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">The M1</span><p id="par0080" class="elsevierStylePara elsevierViewall">These were the first to be identified&#44; they settle in the RGC layer but can appear displaced in the nuclear internal &#40;NI&#41; &#40;M1d&#41;&#59; their number is around 980 per retina and the size of the cellular soma is one of the smallest &#40;14&#8722;16<span class="elsevierStyleHsp" style=""></span>&#956; m&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;29&#44;30&#44;36</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> An M1d has been described&#44; called interneurone melanopsinic&#44; as it lacks an axon in the optic nerve&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> The dendritic tree of M1 is hardly branched&#44; extending in the outermost part of the OFF subslice of the IP &#40;S1&#41; with a diameter of &#8776;300&#8722;350<span class="elsevierStyleHsp" style=""></span> &#956;m<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a> and performs synapses <span class="elsevierStyleItalic">en passant</span> with ON bipolar axons type 6 and with dopaminergic amacrines&#46; During development&#44; a small proportion of M1 and M1d extend their dendrites also to the PE &#40;external retinal dendrites&#41; and there they associate with axonal terminals of the cones&#44; are called biplexiform RGCifs and contribute to the stratification of the retina and lamination of the cones&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">71&#44;72</span></a> In mice and monkeys&#44; a small subgroup of M1 has been described with axonal collaterals that end in PI<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">73&#44;74</span></a> and contribute to the regulation of the adaptation of the retina to light through its connections with dopaminergic amacrines&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a> M1s show little spontaneous activity in the dark and their intrinsic response is very sensitive to light&#44; exhibiting rapid and wide ranging responses&#46; M1s exhibit extrinsic ON responses to light that are small and sustained&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">M1s project approximately 15 brain targets involved in classical NFI visual functions&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> One of the main targets is the SCN&#44; a &#8776;1<span class="elsevierStyleHsp" style=""></span>mm pair nuclei located above the chiasma with a nuclear zone receiving direct retinal afference from the retino-hypothalamic tract and a cortical zone with neurons acting as circadian oscillators&#46; The main retinal afference to the SCN comes from the M1 and to a lesser extent from the M2&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">GCRifs can be differentiated according to the brn3b expression in RGC M1Brn3b- and RGCBrn3b&#43;&#46; The population of RGCif M1Brn3b- &#40;about 200&#41; innervates the SCN and is sufficient to synchronize the circadian rhythm&#44; because when RGCifM1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>are genetically eliminated&#44; most NFI functions are abolished&#44; but circadian synchronization persists&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> The SCN in turn innervates areas involved in mood &#40;ventral tegmental and raphe area&#41; and cognitive functions &#40;hippocampus&#41;&#46; These areas can be influenced through the SCN or directly through a direct pathway of RGCif axons to these nuclei&#44; the medial amygdala and the perihabenular nucleus &#40;PHb&#41;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Both the M1Brn3b- and M1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>project both to the interniculate leaflet and the ventral NGLv region&#44; which are nuclei in charge of prolonging the period of circadian rhythms&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a> The M1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RGCifs profusely innervate midbrain nuclei unrelated to circadian rhythms&#44; nuclei of the thalamus and hypothalamus&#46; The cortex of the PON&#44; involved in the control of the pupil reflex to light&#44;55 is innervated by RGCif M1Brn3b&#43;68&#44; while the nuclear region is primarily innervated by non-M1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RGCif&#46; RGCifM1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>project to the PHb nucleus through the retino-perihabenular pathway&#44; a recently described pathway formed by some 76 RGCif M1 Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>that directly mediate the effects of light on mood&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">The M2</span><p id="par0095" class="elsevierStylePara elsevierViewall">M2s have their somas in the GRC layer&#44; are discreetly larger than the M1 &#40;16&#8722;19<span class="elsevierStyleHsp" style=""></span>&#956; m&#41; and their number is around 830 per retina&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30&#44;40</span></a> The dendritic tree stratifies in the internal sub-layer &#40;ON&#41; of the IP with a diameter of &#8776;316&#8722;324<span class="elsevierStyleHsp" style=""></span>&#956; m and with more regular branches than the M1&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a> They receive afferences of the bipolar ON cone cells type 8&#44; contain significantly less melanopsin than M1 and have a sensitivity to light of an order of magnitude lower than M1&#46; Their extrinsic response is of the broad and sustained ON type&#44; and their receptor field has the classic antagonistic peripheral centre structure&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">M2 projects typical NFI subcortical regions&#44; innervates the SCN and innervates the central region of the PON profusely&#46; They also innervate FI regions&#44; such as NGLd&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;29</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">The M3</span><p id="par0105" class="elsevierStylePara elsevierViewall">M3s are characterised by being biostratified&#44; having one of the largest dendritic tree &#40;457&#8722;497<span class="elsevierStyleHsp" style=""></span>&#956; m&#41; and extend into both sub-layers of the IP&#59; their somas &#40;17&#8722;19<span class="elsevierStyleHsp" style=""></span>&#956; m&#41; sit on the RGC layer and represent less than 10&#37; of the RGCif&#46; The membrane properties and intrinsic responses to light stimulation of M3 are similar to those of M2&#46; The extrinsic responses of M3&#44; similar to those of M2&#44; show a robust response of the ON pathway that induces cellular depolarization&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> This cellular type is scarce and does not form a mosaic that envelops the retina&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> a necessary criterion to consider a different subtype of RGC&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The fate of the M3 projections is not exactly known although it has been suggested that they project the SC<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a> and PHb<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> nuclei&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">The M4</span><p id="par0115" class="elsevierStylePara elsevierViewall">M4s are very sensitive to contrast&#44; they sit in the RGC layer and their shadows are the largest of all RGCifs &#40;19&#8722;24<span class="elsevierStyleHsp" style=""></span> &#956;m&#41;&#46; Their dendritic&#44; radial and highly branched trees grow on the temporonasal axis &#40;210&#8722;420<span class="elsevierStyleHsp" style=""></span>&#956; m&#41;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;77</span></a> and are distributed following a naso-temporal gradient&#44; with a maximum in the super-temporal region&#46; The monostratified dendritic tree in the ON subslice of the IP&#44; discreetly more external than the M2&#44; and probably receives afferences from bipolar cone terminals type 7&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a> M4 lack immunofluorescence against melanopsin detectable with standard techniques&#44; but when the signal is amplified a clear cellular marking appears&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">M4 have intrinsically weak responses that vary according to light adaptation&#59; weak retinal response adapted to light&#44; but greater in adaptation to darkness&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">78</span></a> This intrinsic response of melanopsin contributes to increasing the excitability of the cell and would cause the M4 to fire at very low luminous intensities&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> In knockout mice &#40;Opn4-<span class="elsevierStyleSup">&#41;</span> that do not express melanopsin&#44; deficits in contrast sensitivity due to the lack of melanopsin in M431 can be observed&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The M4 presents extrinsic responses conducted by cones&#44; with large receptor fields organized in center-ON antagonistic periphery-OFF&#44; reminiscent of conventional RGC fields&#44; with sensitivity to movement but without directional selectivity&#46; Recently&#44; it has been documented that when they are recorded adapted to light they present colour opposition&#44; like the M5&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">M4 correspond to the classical sustained RGC&#945; -ON and express non-phosphorylated high molecular weight neurofilaments&#44; osteopontin and calbindin&#44; as well as low levels of melanopsin&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">77&#44;79</span></a> They can be identified by the co-location of non-phosphorylated high molecular weight neurofilaments and calbindine&#44; with SMI32 antibodies and anti-calbindine &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In transgenic mice expressing melanopsin witness with a green fluorescent protein&#44; an average of 570 SMI32&#43;&#47;retin was counted and classified as RGCif M4 &#40;Schmidt et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> 2014&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">M4s overwhelmingly innervate the LGNd ventromedial sector and mediate contrast sensitivity in the absence of cones and rods&#46; In the presence of cones and rods&#44; they also contribute to visual acuity and object tracking&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#8211;31&#44;78</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">The M5</span><p id="par0140" class="elsevierStylePara elsevierViewall">M5s are cells with chromatic opposition which have their soma &#40;12&#8722;16<span class="elsevierStyleHsp" style=""></span>&#956; m&#41; in the GRC layer&#44; with highly branched and compact dendritic trees &#40;149&#8722;274<span class="elsevierStyleHsp" style=""></span>&#956; m&#41; which stratify in the ON subslice of the IP&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;32&#44;77</span></a> They present very weak intrinsic responses&#44; less than the M4&#46; Their immunoreactivity against melanopsin is barely detected with standard techniques and when the signal is amplified&#44; markings can be seen in the soma&#44; but not in the dendrites&#46; M5 have sustained extrinsic ON-type responses&#44; at least an order of magnitude greater than the intrinsic ones&#46; Their particular characteristic is their ultraviolet-green chromatic opposition&#59; the receptor field is constructed so that they have a centre with selective afference of UV cones &#40;through cone bipolars type 9&#41; and mixture of UV and M cones &#40;through cone bipolars types 6&#44; 7 and 8&#41;&#44; and a strong suppressive periphery dominated by M cone afferences through gabaergic amacrines&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> As with other RGCifs&#44; scotopic responses are probably mediated by rod bipolars&#44; AII amacrines &#40;primary pathway&#41; and rod-cone coupling &#40;secondary pathway of the rods&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The M5 project to the LGNd and thus can provide chromatic signals to the visual cortex&#44;32 but it is thought that they can also innervate the PON and the other nuclei innervated by M6&#46; In addition&#44; they project to the intergenic tab which in turn projects to the SCN&#44; suggesting a pathway for M5 to provide chromatic information to the spectral opposition neurons of the SCN&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">The M6</span><p id="par0150" class="elsevierStylePara elsevierViewall">M6s are spiny bistable cells that settle in the RGC layer&#46; Both the soma &#40;11&#8722;15<span class="elsevierStyleHsp" style=""></span>&#956; m&#41; and its highly branched dendritic tree &#40;190&#8722;250<span class="elsevierStyleHsp" style=""></span>&#956; m&#41; are the smallest of all RGCifs&#46; In retinas of pigmented Cdh3-GFP transgenic mice a few dozen M6 RGCifs were counted&#44; a figure that may underestimate the real magnitude of this subtype since in this mouse they are only marked in the ventral retina&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The external dendritic branch extends to the distal margin of the IP&#44; close to the NI&#44; where they stratify the M1 and the external tree of the M3&#46; The internal dendritic branch accounts for approximately 85&#37; of the dendritic volume and extends to the internal margin of the IP&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> M6 express very low levels of melanopsin detectable with tyramid amplification techniques and when staining appears it can be observed as patches in the soma region&#44; but not in dendrites&#46; M6 have very weak intrinsic responses&#44; which are lower than M4 and M5&#46; The M6 have sustained ON-type responses when their entire relatively small and strongly antagonistic centre-periphery receptor field is illuminated&#46; Although they have part of their dendritic tree in the OFF region of the IP&#44; their responses are&#44; like those of all RGCifs&#44; of the sustained ON type&#46; It is thought that the external dendritic tree receives in the OFF subslice of the IP ectopic afferences <span class="elsevierStyleItalic">en passant of</span> bipolar axons ON&#46; These cells lack colour response and directional selectivity&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">On the one hand&#44; the M6 projects to typical NFI territories such as the centre of the PON&#44; the pretectal posterior nucleus&#44; the intergeniculated leaflet and NGLv and&#44; on the other hand&#44; projects weakly to the NGLd&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Inherently photosensitive retinal ganglion cells in primates and humans</span><p id="par0160" class="elsevierStylePara elsevierViewall">In humans&#44; the total number of RGCif varies between 0&#46;2&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> 0&#46;4&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> 0&#46;8<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;62&#44;82</span></a> and 1&#46;5&#37;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">83</span></a> of the RGC population&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">84</span></a> These variations are due to technical differences in detecting melanopsin&#44; as well as to the lower expression of melanopsin in M2 and M4&#44; compared with M1&#46; As in rodents&#44; melanopsin is expressed in a more abundant short isoform&#44; present in M1 and M3&#44; and a long isoform present in all melanopsins&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The somas and dendritic trees of the RGCm<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>of the retinas of humans and macaques are among the largest&#46; Initially&#44; these RGCifs were classified according to their stratification in the OFF and ON subslices of the IP into external and internal RGCifs&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;59&#44;81&#44;82</span></a> More recently&#44; using antibodies against the N and C terminals of human melanopsin&#44; Hannibal et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> &#40;2017&#41;&#44; based on the location and size of the soma and on the stratification of their dendritic trees&#44; classified RGCifs according to the nomenclature used in rodents&#46; The predominant type in humans is M1&#44; with a high proportion of displaced cells &#40;dM1&#41; and with higher expression of melanopsin&#46; One type of giant M1 &#40;GM1&#41;&#44; which projects the nGDL&#44; exhibits an opposing response to the yellow-ON blue-OFF colour&#44; mediated by S-OFF cones antagonized by a cone response &#40;L<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>M&#41;-ON&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> involving recently described amacrine cells that receive from bipolar S-ONcones&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a> Displaced giants GM1d were also identified&#46; Some of the M1s had axonal collaterals that extended into the retina&#46; The M2s &#40;known as internal&#41; are less abundant and express less melanopsin&#46; In humans&#44; there are also RGCifs similar to M3s that stratify at S1 and S5&#44; but their frequency is very small and their characterisation very poor&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">62&#44;82</span></a> They have also been described in M4 humans&#44; distributed in the naso-temporal axis and with higher density in the temporal hemiretina&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a> To date it is not known whether the human and primate retina has M5 and M6&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The distribution of M1 in humans contrasts with that of M1 in rodents&#44; since in humans and primates they have very high densities in the central perifoveal region and lower densities in the periphery&#44; whereas M2 are less abundant and are distributed similarly to M4&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">62&#44;84</span></a> This different density of RGCif in the perifoveal and peripheral region may mean a different function in the perception of colour opposition&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In the primate&#44; RGCif projections have been studied by combining a very sensitive antegrade tracer&#44; the choleric B toxin subunit and immunohistochemistry to reveal the presence of PACAP&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">86</span></a> The presence of PACAP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>terminals was documented in regions supporting visual NFI functions&#46; Thus&#44; primate RGCifs densely project the SCN&#44; PON and pregeniculate complex &#40;which corresponds to the intergeniculate tab of the rodent&#41;&#46; In the pretectal region&#44; they also showed dense innervation in the nucleus of the optical tract but scarce innervation in the posterior medial pretectal nucleus&#46; Doubly marked fibres have also been observed in regions supporting visual functions FI&#44; the <span class="elsevierStyleItalic">brachium of the</span> SC and the visual layers of the SC&#44; as well as in lateral geniculated nucleus in the corresponding contralateral &#40;1&#44; 4 and 6&#41; or ipsilateral &#40;2&#44; 3 and 5&#41; layers&#44; in the main regions &#40;parvo or magno&#41; but not in the koniocellular ones&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Contribution of intrinsically photosensitive retinal ganglion cells to non-image-forming visual functions</span><p id="par0175" class="elsevierStylePara elsevierViewall">In mice&#44; ablation of RGCifs<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26&#44;87</span></a> causes the loss of NFI visual functions with maintenance of classic vision and conventional RGCifs&#44; indicating that RGCifs constitute the functional unit of the NFI system&#44; which transmits to the brain the information obtained from both classic photoreceptors and melanopsin activation&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">88</span></a> The NFI functions consist mainly of <span class="elsevierStyleItalic">1&#41;</span> the daily synchronisation of our circadian rhythms&#59; <span class="elsevierStyleItalic">2&#41;</span> regulation of the photomotor reflex&#59; 3&#41; regulation of our sleep-wake rhythms&#59; 4&#41; regulation of body temperature&#59; 5&#41; regulation of metabolic activity&#59; 6&#41; regulation of our cognitive abilities and mood&#59; <span class="elsevierStyleItalic">7&#41;</span> aversion to light&#59; and <span class="elsevierStyleItalic">8&#41;</span> adaptation of the retina to light&#46;</p><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Synchronisation of circadian rhythms</span><p id="par0180" class="elsevierStylePara elsevierViewall">The synchronisation of our circadian rhythms consists in the timing of our central circadian pacemaker&#44; located in the SCN&#44; which receives direct information from the retina through the retino-hypothalamic tract&#44; mainly innervated by RGCif M1&#46; All the species studied have circadian rhythms &#40;which oscillate in a period of 24<span class="elsevierStyleHsp" style=""></span>h&#59; circa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>approximate&#59; day<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h&#41; governed by a main pacemaker&#44; which imposes its own rhythm even in constant light conditions&#44; but which is delayed a little every day&#46; These pacemakers are synchronised with time keys and in our case sunlight acts as a timer to set our circadian pacemaker on time&#46; The synchronisation of the circadian rhythm depends on a subpopulation of 200 M1Brn3b-4&#44; and disappears in animals that lack the retino-hypothalamic tract&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">89</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Circadian synchronisation directly modulates the rhythms of many physiological functions such as appetite&#44; temperature cycles and the level of circulating hormones&#44; which in turn synchronises clocks present in many tissues of the body&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">90</span></a> In addition to regulating circadian rhythms&#44; the SCN also acts as a relay station to conduct light information to other territories that receive direct input from the RGCif&#44; thus providing an indirect pathway for functions related to sleep&#47;wakefulness&#44; our cognitive abilities and mood&#46; The secretion of melatonin&#44; which modifies our cardiac rhythms&#44; and the suppression of motor activity are examples of this concept&#59; although they are regulated in a circadian way&#44; they are also suppressed in an acute way by exposure to light &#40;known as masking&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> an effect mediated by direct afference to the ventral nucleus of the sub-ventricular zone&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a> and it is thought that the same RGCifs that innervate the SCN are responsible for both behaviours&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Pupillary reflex to light</span><p id="par0190" class="elsevierStylePara elsevierViewall">One of the classic NFI functions is the regulation of the pupillary reflex to light by the PON innervated in its cortex by the M2 and other non-M1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RGCifs and in its centre by M1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RGCifs&#46; The photomotor reflection is performed by the 3 types of photoreceptors&#46; Typical rapid and broad responses at the beginning of the stimulus depend on cones and rods&#44; while sustained responses following acute responses depend on melanopsin&#46; This has been documented in mice lacking cones and rods &#40;rd&#47;rd cl&#41;&#44; which had slow but durable responses&#44; coming from RGCifs&#44; and in knock-out mice &#40;Opn4-&#47;-&#41; lacking intrinsic melanopsin-mediated responses<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> that had rapid transient responses&#44; with no response to high irradiances&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> In triple knock-out mice&#44; which do not express melanopsin and have altered phototransduction of rods and cones &#40;Gnat1-&#47;-&#59; Cnga3-&#47;-&#59; Opn4-&#47;-&#41;&#44; a normal retina is observed&#44; but total absence of pupillary response to light&#44; circadian compliance&#44; suppression of motor activity or any other of the typical NFI functions triggered by light&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Similar results were obtained from mice in which RGCif had been genetically ablated&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> In humans&#44; the contribution of the different photoreceptors has been examined using chromatic pupillometry which quantifies the photomotor reflex based on the spectral sensitivity of each photoreceptor&#59; the different components of this reflex have been described&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">91</span></a> After the presentation of light a phasic response is produced&#44; of rapid appearance and short duration&#44; with a robust contraction of the pupil mediated by rods and cones&#46; Subsequently&#44; the pupil gradually relaxes to a more dilated state and if the intensity of light exceeds the melanopsin activation threshhold&#44; the pupil remains contracted to a constant size&#44; this response is called the post-phase response&#46; If the light has been maintained for more than 3<span class="elsevierStyleHsp" style=""></span>min&#44; when the light is switched off the pupil constriction persists for a few seconds before relaxing to normal values&#44; and this is called the post-lighting pupil response &#40;PLPR&#41;&#44; which is melanopsin-dependent&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">67&#44;91&#44;92</span></a> The PLPR are added binocularly when the stimulus is presented binocularly<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">93</span></a> and do not appear to be directly influenced by colour&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">94</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Sleep&#47;Wake rhythms</span><p id="par0195" class="elsevierStylePara elsevierViewall">It was thought that sleep-wake cycles were regulated indirectly through our circadian rhythms&#44; but it has been documented that Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RGCifs send direct intrinsic and extrinsic information to the lateral hypothalamus region and ventrolateral preoptic area to regulate both the onset and duration of the sleep cycle&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6&#44;67&#44;95</span></a> It is not yet known exactly which of the 6 types of RGCif Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>is responsible for the regulation of these rhythms&#44; but it has been suggested that it would be the M1 or M2 that express the highest levels of melanopsin&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Body temperature rhythms</span><p id="par0200" class="elsevierStylePara elsevierViewall">Body thermoregulation follows circadian rhythms and its control has been attributed to the function of the central pacemaker of the SCN&#46; Today we know that the SCN performs circadian control of body temperature with the afferent information that reaches it through the M1Brn3b- RGCifs&#44; but that the Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RGCifs are necessary for direct acute control of body temperature&#59; for example&#44; after the presentation of a night-time light pulse&#46; Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RGCifs are thought to exert their effect through direct projections to the preoptic median and ventrolateral nuclei of the hypothalamus&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Regulation of metabolic activity</span><p id="par0205" class="elsevierStylePara elsevierViewall">The daily metabolic activity is adapted to the circadian rhythms imposed by the light-darkness cycles&#46; This activity is controlled by hypothalamic nuclei containing pacemakers which are in turn regulated by the central pacemaker of the SCN&#46; In mice with selective hypomorphic Pitx3 expression&#44; where the retino-hypothalamic tract is absent&#44; there is a mismatch between the SCN pacemakers &#40;responsible for circadian rhythms&#41; and the ventromedial hypothalamus &#40;responsible for energy intake and balance rhythms&#41; resulting in behavioural and metabolic alterations that affect locomotor activity&#44; feeding and energy expenditure rates&#44; and corticosterone secretion&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">89</span></a> These alterations are thought to be due to the lack of maturation of the SCN pacemaker during development due to the lack of retinal afferences&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">56&#44;89&#44;96</span></a></p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Mood and cognitive abilities</span><p id="par0210" class="elsevierStylePara elsevierViewall">The effect of light in the modulation of our moods and intellectual capacity is well known&#46; For example&#44; a flight that crosses several time zones decouples our circadian rhythm from solar time <span class="elsevierStyleItalic">&#40;jet lag&#41; and</span> takes a few days to become regularized&#46; During these days&#44; we experience alterations in our sleep&#47;wake rhythm&#44; cognitive deterioration&#44; discomfort and irritability that disappear when our circadian rhythm is again in step with local solar time&#46; This type of alteration is also experienced by workers who run shifts &#40;alternating day&#47;night shifts&#41;&#44; at night&#44; or in those who suffer from seasonal affective disorder that appears in late autumn and during the winter as a result of the rapid shortening of daylight hours&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a> Classically&#44; it was thought that both the regulation of cognitive functions and mood depended on SCN&#46; Today it is known that SCN indirectly influences these functions&#44;65 but that there are 2 different RGCifs projections directly responsible for these functions&#46; On the one hand&#44; a subpopulation of approximately 71 RGCif M1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>that innervate the thalamic nucleus PHb &#40;retinal-habdominal pathway&#41; is directly responsible for the modulation of mood&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Furthermore&#44; these RGCifs that inervate the nucleus PHb emit collaterals that project to the dorsal and ventral striatum and to the prefrontal cortex&#46; All of these nuclei are involved in the control of affective-emotional processes&#44; mood and depression&#44; and mood regulation and depressive disorders&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">On the other hand&#44; the M1Brn3b RGCifs<span class="elsevierStyleSup">&#8213;</span> &#40;approximately 200&#41; that innervate the SCN are responsible for the modulation of cognitive abilities&#44; independently of the synchronisation of the circadian rhythm&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> although the innervated nuclei responsible for these abilities are unknown&#46; For example&#44; mice lacking RGCif M1Brn3b<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>showed normal cognitive and learning functions in tests of recognition of new objects and the Morris water labyrinth&#44; thus documenting that the absence of this subpopulation does not affect the cognitive functions of these animals since they are mediated by RGCif M1Brn3b-&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Aversion to light</span><p id="par0220" class="elsevierStylePara elsevierViewall">Light aversion&#44; i&#46;e&#46; the distant displacement of light&#44;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">97</span></a> is a reflex sensory response that is observed in neonatal mice as soon as P6&#44; a period in which the only sensitivity to light is produced by the activation of RGCifs&#44; long before signals from cones and rods begin to be produced and sent to the RGCifs&#46; In Opn4-&#47;- neonatal mice no light aversion is seen&#44; indicating that melanopsin is necessary for light aversion&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">98</span></a> This behaviour is mediated by the SC&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">99</span></a> so it is probable that it is due to the afferences of the RGCif not M1&#44; since they are the only ones that innervate the SC at these postnatal ages&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">100</span></a></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Adaptation of the retina to light</span><p id="par0225" class="elsevierStylePara elsevierViewall">A small population of RGCif M1 Brn3b- has intraretinal axonal collaterals that project to the external retina&#44;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">73&#44;74</span></a> transmitting luminance signals through the dopaminergic system and thus influencing the adaptation of the retina to light&#44; enabling it to operate at illumination levels comprising 10 logarithmic units&#46; The M1 excitation signal causes the secretion of dopamine by dopaminergic amacrines<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">74&#44;101</span></a> which form an intraretinal feedback pathway transmitting cone&#44; rod and RGCif signals in a centrifugal direction from the inner to the outer retina&#46; The released dopamine exerts its action through D1-D5 dopamine receptors and the activation of these modifies retinal circuits according to the prevailing lighting&#59; that is&#44; electrical decoupling through the retina&#44; modulating the glutamate exciter receptors in the horizontal ones and regulating the activity of the sodium channels of the RGC and bipolar channels&#46; The depletion of dopamine in the retina results in an alteration in the adaptation of our vision to light&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">102</span></a></p></span></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Contribution of intrinsically photosensitive retinal ganglion cells to visual image-forming functions</span><p id="par0230" class="elsevierStylePara elsevierViewall">The discovery of new RGCif subtypes in mice and primates that projected the LGNd and SC&#44; nuclei directly involved in FI and conscious visual perception&#44; suggested the participation of RGCif in FI visual functions&#46; Gnat1-&#47;-&#59; Cnga3-&#47;- mice&#44; which lack functional rods and cones and depend on melanopsin for light detection&#44; showed gross visual behaviours which required approximately twice as much time as control mice to pass visual tests&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> These visual abilities disappeared in triple knock-out mice &#40;Gnat1-&#47;-&#59; Cnga3-&#47;-&#59; Opn4-&#47;-<span class="elsevierStyleSup">&#41;&#44;</span> which lacked any kind of functional photoreception&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Subsequent studies have documented that mice lacking in melanopsin &#40;Opn4-&#47;-&#41;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> or lacking in CFRif M4 &#40;Opn4<span class="elsevierStyleSup">Cre&#47;&#43;</span>&#59; Bnr3b<span class="elsevierStyleSup">zDTA&#47;&#43;</span> mice&#41;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> show deficits in contrast sensitivity both in subcortical &#40;optokinetic tracking&#41; and cortical &#40;visual water labyrinth&#41;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">103</span></a> behavioural visual tasks&#44; showing that the melanopsin in these cells influences their physiological properties&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">It is now accepted that RGCifs contribute to contrast detection&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> light intensity discrimination&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> adaptation of LGNd activity according to irradiance<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;104</span></a> and spatial pattern coding&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;34</span></a> Using techniques to present images that independently modulate the visibility of melanopsin vs&#46; cones and rods&#44; evoked responses of LGNd were recorded in control animals of which 20&#37; responded to patterns visible only by melanopsin&#46; Melanopsin signals have sufficient spatial-temporal resolution to encode spatial patterns&#44; a modest spatial resolution with receptor fields from &#8776;13&#176; and a modest temporal frequency &#8776;1<span class="elsevierStyleHsp" style=""></span>Hz&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">The colour of light in circadian synchronisation</span><p id="par0240" class="elsevierStylePara elsevierViewall">The synchronisation of the circadian rhythms to the light&#47;darkness cycles not only takes into account the information on oscillations in light intensity&#44; but also its colour variations&#46; As twilight develps there is a progressive enrichment of short wave light&#46; This is due to the filtering of long wavelength light by the Chappuis band of the ozone layer &#40;Chappuis filter effect&#41; when the sun is below the horizon&#44; at a time of day when the sky is particularly blue &#40;the blue hour&#41; and which is observed both at the end of twilight and at the beginning of dawn&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">105</span></a> In the SCN&#44; &#8776;25&#37; of the neurons recorded intracellularly are sensitive to spectral changes with cone-dependent opposite colour responses&#44; most with blue-ON&#47;yellow-OFF responses and a minority with yellow-ON&#47;blue-OFF responses&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> The light colour information allows the SCN to obtain accurate information about the time of transition&#44; twilight or dawn&#44; and thus to achieve a more reliable time setting of the circadian pacemaker as well as allowing the SCN to distinguish a decrease in irradiance because the sky has become cloudy&#44; from the decrease that occurs at dusk or dawn&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">106</span></a> It has been postulated that the use of colour to accurately determine the onset of phase change of our circadian rhythms could be an evolutionarily conserved strategy and perhaps one of the original purposes of colour vision&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> In rodents&#44; it has been suggested that the M5&#44; characterized by its chromatic opposition&#44; could inform the SCN of spectral variations through its afferences to the intergeniculate tongue&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> In primates&#44; chromatic RGCif GM1 &#40;blue-OFF&#47;yellow-ON&#41;<span class="elsevierStyleSup">21</span> has been described and recently it has been documented that this information could be mediated by the afferences of the bipolar S-ON cone to a new amacrine cell that receives excitatory afferences from the bipolar S-ON cone and&#44; in turn&#44; makes inhibitory contacts in RGCif M1 resulting in a blue-OFF85 response&#46; These RGCif M1 with S-OFF responses of primates could be the SCN afference for the tuning of the circadian clock setting at dawn and dusk&#44; when the highest colour contrasts of light occur&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a></p></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Non-image-forming visual functions in the disease</span><p id="par0245" class="elsevierStylePara elsevierViewall">Clinical studies carried out on neurodegenerative diseases have documented alterations in the melanopathic pathway associated with anomalies in visual functions NFI82<span class="elsevierStyleSup">&#44;84</span>&#46; Thus&#44; patients with Parkinson&#39;s disease exhibit a significant decrease in the RGCif population that could be responsible for the alterations in mood and sleep&#47;wake cycles reported in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">107</span></a> Similarly&#44; in retinas of older donors &#40;&#62; 70 years&#41; a decrease in RGCif density and atrophy of their dendritic trees was observed that could also be related to alterations in circadian rhythms observed in the elderly&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">108</span></a> In a study carried out on the retinas of patients with Alzheimer&#39;s disease&#44; degeneration of RGCif and alterations in their dendritic trees were documented&#44; and these findings were correlated with alterations in circadian functions&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">109</span></a> In a study carried out on completely blind patients with total absence of light perception due to different causes &#40;retinitis pigmentosa&#44; retinopathy of prematurity&#44; retinopathies due to retinitis or rubella syndrome&#44; congenital glaucoma&#44; neuropathy or optic neuritis&#44; or unknown causes&#41; it was documented that a small fraction of these &#40;&#8776;33&#37;&#41; showed suppression of melatonin secretion when exposed to light&#44; suggesting the preservation of circadian rhythms and the persistence of the retinohypothalamic tract&#46; This observation was&#44; however&#44; absent in the 3 patients of the study that had undergone bilateral enucleation&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">110</span></a> Another study examined the prevalence of circadian alterations in 123 blind women without or with light perception&#44; studying alterations in sleep&#47;wakefulness rhythms and the rhythm of melatonin secretion by examining the sleep&#47;wakefulness diary of these patients&#44; as well as the urinary excretion every 4&#8722;8<span class="elsevierStyleHsp" style=""></span>hours of 6-sulfatoximelatonin&#44; the main urinary metabolite of melatonin&#46; Most of the participants without any perception of light &#40;&#8776;63&#37;&#41; had abnormalities in their circadian rhythms or were not in sync&#46; These were patients with bilateral enucleations or retinopathy of prematurity&#46; The majority of participants with light perception &#40;&#8776;69&#37;&#41; had normal circadian rhythms and were patients with retinitis pigmentosa or age-related macular degeneration&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">111</span></a></p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Visual functions of intrinsically photosensitive retinal ganglion cells in the postnatal period</span><p id="par0250" class="elsevierStylePara elsevierViewall">In rats and mice&#44; RGCifs are present in the retina from birth &#40;P0&#41; and show photosensitive responses long before the cones and rods begin to function and send their signals to the retina&#44; which roughly coincides with the eye opening &#40;P10&#41;&#46; RGCifs were identified and classified in records made in the postnatal retina &#40;P10-12&#41; according to their latency&#44; sensitivity and intensity of response to light at 3 types&#58; I&#44; the most frequent 78&#37;&#59; II &#40;15&#37;&#41; and III &#40;13&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">112</span></a> Electrophysiological records and the combined use of anti-melanopsin antibodies and SMI32 &#40;an antibody against the high molecular weight non-phosphorylated subunit of the neurofilaments triplet&#41; have allowed the classification of these postnatal RGCifs and their association with adult types&#46; Thus&#44; type I &#40;m<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>SMI32<span class="elsevierStyleSup">&#43;</span>&#41;&#44; II and III &#40;m<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>SMI32<span class="elsevierStyleSup">&#8722;</span>&#41; RGCifs correspond to M4&#44; M2 and M1&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">96&#44;113</span></a> These RGCifs decrease both in number and in photosensitivity during early postnatal development until adulthood&#44; which is mainly due to the reduction and death of melanopsin M4 RGCifs expression&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">114</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">The functions of RGCifs during early postnatal development are <span class="elsevierStyleItalic">1&#41; to</span> regulate the development of the pattern of vascular branching in the retina and the regression of the embryonic hyaloid vasculature&#59; mice lacking melanopsin &#40;Opn4-&#47;-<span class="elsevierStyleSup">&#41;</span> show abnormal vascular development and hyaloid regression<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">115</span></a>&#59; <span class="elsevierStyleItalic">2&#41;</span> the aversion to light of neonatal mice &#40;P6&#41;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;98</span></a>&#59; <span class="elsevierStyleItalic">3&#41;</span> the inter-RGCif coupling necessary to produce the waves of spontaneous retinal activity<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">116</span></a> that regulate the refinement of ocular segregation of axonal retinal terminals in the geniculate and SC&#59; the M1 Brn3b- RGCifs regulate the triggering properties of RGCs through signals by their intraretinal axonal collaterals<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a>&#59; <span class="elsevierStyleItalic">4&#41; the</span> maturation of the circadian rhythm&#44; i&#46;e&#46; the establishment of the duration of the circadian rhythm phases&#59; the subgroup of 200 RGCif M1Brn3b<span class="elsevierStyleSup">&#8722;</span> which exclusively projects the SCN&#44; is responsible for the maturation of the circadian clock and the initial establishment of the duration of the phases<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">56&#44;96&#44;117</span></a> and <span class="elsevierStyleItalic">5&#41;</span> the organisation of the retinal architecture and the lamination of the cones&#46; Opn4DTA&#47;DTA mice lacking RGCif showed a disorganisation of the cones at P7 and P16&#44; and an anomalous displacement of these to other layers of the retina&#46; In these mice it was documented that light during the first postnatal week contributes to restrict the somas of the cones to the external nuclear and influences the lamination of the cones to their layer&#46; It has been postulated that in these mice the RGCif use their external dendrites to communicate with the cones and regulate the number of cones displaced outside the NE&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Melanopsin phototransduction</span><p id="par0260" class="elsevierStylePara elsevierViewall">Opsins are receptors coupled to a G-protein that convert the energy of a photon into a change of the membrane potential&#46; Visual pigments consist of an apoprotein &#40;the opsin&#41; to which a chromophore molecule&#44; a derivative of vitamin A1&#44; 11-cis-retinaldehyde&#44; is attached&#46; Small changes in the structure of the protein change the absorption spectrum&#46; Melanopsin is a visual pigment with a &#955;<span class="elsevierStyleInf">max</span> of 480<span class="elsevierStyleHsp" style=""></span>nm&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The efficiency of melanopsin is comparable to cone and stick opsins&#44; but there are differences between melanopsin phototransduction and classical opsins&#58; <span class="elsevierStyleItalic">1&#41;</span> phototransduction in cones and rods results in a transient hyperpolarisation and&#44; as a consequence&#44; the signal transmitted in the synaptic foot is a reduction of glutamate release&#59; the phototransduction cascade of melanopsin is more similar to that of invertebrates and results in membrane depolarisation &#40;Graham et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">118</span></a> 2008&#41; and consequently there is an increase in the frequency of action potentials dependent on ambient lighting<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">69&#44;119</span></a>&#59; <span class="elsevierStyleItalic">2&#41;</span> the melanopsin phototransduction cascade is much slower<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">120</span></a>&#59; <span class="elsevierStyleItalic">3&#41;</span> RGCifs lack cellular specialisations &#40;discs and saccules&#41; that have rods and cones to optimise the chances of capturing a photon&#44; resulting in a difference in molecule density&#47;unit area of 8&#46;300 times greater in cones and rods with respect to RGCifs and&#44; therefore&#44; less probability of absorption of one photon per photo-stimulation area for RGCifs&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a> However&#44; melanopsin can be activated in scotropic conditions&#44; which confers great sensitivity to the melanopsin system<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">121</span></a>&#59; <span class="elsevierStyleItalic">4&#41;</span> the amplification of the melanopsin phototransduction cascade compensates for the low amount of melanopsin and the few photons that are absorbed&#59; once the melanopsin activation threshold is reached&#44; the response persists during long periods of constant illumination&#59; it has been documented in in vitro studies that the melanopsin signal can remain active for 10 continuous hours of light<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">122</span></a>&#59; <span class="elsevierStyleItalic">5&#41;</span> regeneration of the visual pigment is thought to occur by a light-dependent mechanism&#59; photo-exposed melanopsin is converted to metamelanopsin which retains the chromophore in the all-trans form and after absorption of a new photon regenerates the 11-cys form&#44; thus RGCifs do not discolour regardless of how much light they are exposed to&#59; these are called bistable pigments because they have an intrinsic regeneration mechanism that makes them resistant to discolouration&#44; similar to invertebrates&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">92&#44;123</span></a> It is not known whether M&#252;ller cells act as a chromophore reservoir for melanopsin&#44;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">101</span></a> and <span class="elsevierStyleItalic">6&#41;</span> it was thought that melanopsin phototransduction employed similar mechanisms in all RGCifs and that those expressing little melanopsin &#40;M4-M6&#41; owed their primary function to their extrinsic afferences&#44; relegating the function of their small amount of melanopsin to second place&#46; However&#44; it has been documented that the intracellular melanopsin cascade uses different mechanisms in different types of RGCif<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> and that in RGCifs involved in FI functions melanopsin&#44; although low&#44; can modulate the processing of signals from rods and cones&#46; For example&#44; increasing the contrast sensitivity of M4s involved in spatial vision in a range of lighting from very high to very low levels involving only rods&#44; using potassium permeable channels to increase the excitability of M4&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a></p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Final considerations</span><p id="par0270" class="elsevierStylePara elsevierViewall">RGCifs are characterised by their intrinsic response to melanopsin&#44; but they also have extrinsic responses mediated by classical photoreceptors through the same circuits as conventional RGCifs&#44; so that the melanopsin pathways integrate all the light signals captured by the retina&#46; So&#44; why do RGCis want these integrated afferences&#63; One possible explanation would be to extend their range of action&#44; since they inform the brain of very faint light signals &#40;which activate the rods&#41;&#44; moderate &#40;in which the cones with a faster kinetic signal participate and also inform about colour&#41;&#44; up to very high and maintained levels &#40;which activate the melanopsin&#41;&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Is the classification of RGCif according to its NFI and FI functions still valid&#63; The classification of RGCifs as responsible for NFI visual functions has been useful to study these functions in detail&#44; but as more has been learned about these cells it has become clear that the original division in RGCifs responsible for NFI and FI functions is not as clear&#46; Many M1Brn3b<span class="elsevierStyleSup">&#43;</span> RGCifs project nuclei responsible for NFI &#40;e&#46;g&#46;&#44; PON&#41; and FI &#40;e&#46;g&#46;&#44; LGNd regions&#41; vision functions&#46; Even a single subpopulation of RGCif M1Brn3b- that is primarily devoted in adults to NFI &#40;circadian rhythm synchronisation&#41; visual functions&#44; during early to mid postnatal development&#44; however&#44; refinement of FI visual functions &#40;axonal segregation in the LGNd&#41; and NFI visual functions &#40;such as establishment of the time period of circadian rhythms&#41;<span class="elsevierStyleSup">56</span>&#46; Schematically&#44; this classification could be summarised in that the M1Brn3b<span class="elsevierStyleSup">&#8722;</span> have primarily NFI functions related to circadian rhythms&#44; while the M1Brn3b<span class="elsevierStyleSup">&#43;</span> have mostly non-circadian NFI functions with a very small contribution to FI functions&#59; the M2&#44; also Brn3b<span class="elsevierStyleSup">&#43;</span>&#44; would be responsible for NFI visual functions &#40;the photomotor reflex&#41; and FI visual functions&#44; while the M3-M6&#44; all Brn3b<span class="elsevierStyleSup">&#43;</span>&#44; would be mostly responsible for FI visual functions&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">Could we ignore a RGCif population as small as the M4-M6&#63; The mammal&#39;s brain in general has very little redundancy&#46; However&#44; and neural populations that may seem insignificant perform crucial functions&#46; For example&#44; we know that as few as about 70 M1Brn3n<span class="elsevierStyleSup">&#43;</span> RGCifs form the retino-perihabenular pathway and are responsible for mood&#44; which is substantially modified by irregular exposures to light during normal day&#47;night cycles&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Furthermore&#44; it has recently been documented that the melanopsin in RGCif M4 is able to modulate its excitability in a very wide range of lighting conditions&#44; increasing its sensitivity to contrast&#46; This effect is produced in M4 cells by a mechanism never before associated with melanopsin&#44; consisting of the closure of potassium leakage channels &#40;potassium channels of the TASK subfamily&#44; of the double pore domain potassium channel family&#44; K2P&#41;&#44; which is selective from the RGCifs involved in FI &#40;Sonoda et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> 2018&#41;&#46; As this mechanism is not present in M1&#44; it has been suggested that the melanopsin phototransduction cascade would act with different mechanisms on different types of RGCif&#46; Melanopsin would be able to enhance the visual signal of M4 RGCifs&#44; which encode FI&#44; in a range of luminance that vary from a dim light that activates only rods to a more intense light that preferentially activates cones&#44; thus modulating visual processes in much greater ranges than previously thought&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">In short&#44; RGCifs have many features that distinguish them from the more conventional RGCifs&#58; <span class="elsevierStyleItalic">1&#41; RGCifs</span> perform a wide range of functions&#59; to the increasingly well understood NFI functions we must add the knowledge of the FI functions performed by M4&#44; while the exact role of M5 and M6 has yet to be deciphered&#59; <span class="elsevierStyleItalic">2&#41;</span> RGCifs express very different amounts of melanopsin&#44; high in M1&#44; moderate with an order of magnitude lower in M2-3&#44; or barely noticeable with 2 orders of lower magnitude in M4-6&#46; However&#44; independently of the amount of melanopsin&#44; their expression confers on them a very particular functional singularity&#59; <span class="elsevierStyleItalic">3&#41;</span> in general&#44; RGCs functionally respond to light stimuli depending on the sublaminate of the IP in which they extend their dendrites&#44; external &#40;a&#44; OFF&#41; or internal &#40;b&#44; ON&#41;&#44; so that RGCs that branch out in the external or internal sublaminate have responses of centre-OFF &#40;decrease of discharges in the presence of light&#41; or centre-ON &#40;increase of discharges in the presence of light&#41;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">124</span></a> However&#44; RGCif M1&#44; M3 and M6&#44; in spite of extending their dendrites in the OFF sublaminamte&#44; have the peculiarity that their responses are of the ON type&#44; as the rest of the RGCifs&#46; These are produced because M1&#44; M3 and M6 receive in the OFF subslice ectopic afferences <span class="elsevierStyleItalic">en passant</span> of bipolar ON&#44; which has led to think that this region of the IP could be considered an additional subdivision of the OFF subslice that informs the RGCif ON&#44; and <span class="elsevierStyleItalic">4&#41;</span> finally&#44; and although it has not been the subject of this review&#44; the RGCif exhibit particular resilience to multiple types of retinal injury that makes them particularly resistant to injuries&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;43&#44;45&#44;49</span></a> In summary&#44; it is therefore a type of RGCif&#44; one of the 40 possible types&#44; which is actually composed of 6 subtypes&#44; which still has many unknown issues and will undoubtedly continue to contribute to maintain the melanopsynic system as one of the most active fields of research in vision&#46;</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Funding</span><p id="par0290" class="elsevierStylePara elsevierViewall">This work has been party financed by the <span class="elsevierStyleGrantSponsor" id="gs0005">Seneca Foundation&#44; Science and Technology Agency Region of Murcia</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0005">19881&#47;GERM&#47;15</span>&#41; and by the <span class="elsevierStyleGrantSponsor" id="gs0010">Ministry of Economy and Competitiveness&#44; Carlos III Health Institute&#44; European Regional Development Fund &#8220;a way of making Europe&#8221;</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0010">SAF2015-67643-P</span>&#59; <span class="elsevierStyleGrantNumber" refid="gs0010">PID 2019-106498GB-I00</span>&#59; <span class="elsevierStyleGrantNumber" refid="gs0010">RD16&#47;0008&#47;0004</span>&#59; <span class="elsevierStyleGrantNumber" refid="gs0010">RD16&#47;0008&#47;0016</span>&#41;&#46;</p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conflict of interest</span><p id="par0295" class="elsevierStylePara elsevierViewall">No conflict of interest was declared by the authors&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:19 [
        0 => array:3 [
          "identificador" => "xres1520846"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1379101"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1520845"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1379100"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "The retina"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Imaging and non-imaging paths"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Retinal ganglion cells"
        ]
        7 => array:3 [
          "identificador" => "sec0020"
          "titulo" => "Inherently photosensitive retinal ganglion cells"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "General characteristics of intrinsically photosensitive retinal ganglion cells"
            ]
            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Number and distribution of intrinsically photosensitive retinal ganglion cells"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "General projections of intrinsically photosensitive retinal ganglion cells"
        ]
        9 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Morphological characteristics and projections of intrinsically photosensitive retinal ganglion cells"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "The M1"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "The M2"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "The M3"
            ]
            3 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "The M4"
            ]
            4 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "The M5"
            ]
            5 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "The M6"
            ]
            6 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Inherently photosensitive retinal ganglion cells in primates and humans"
            ]
          ]
        ]
        10 => array:3 [
          "identificador" => "sec0080"
          "titulo" => "Contribution of intrinsically photosensitive retinal ganglion cells to non-image-forming visual functions"
          "secciones" => array:8 [
            0 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Synchronisation of circadian rhythms"
            ]
            1 => array:2 [
              "identificador" => "sec0090"
              "titulo" => "Pupillary reflex to light"
            ]
            2 => array:2 [
              "identificador" => "sec0095"
              "titulo" => "Sleep&#47;Wake rhythms"
            ]
            3 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Body temperature rhythms"
            ]
            4 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Regulation of metabolic activity"
            ]
            5 => array:2 [
              "identificador" => "sec0110"
              "titulo" => "Mood and cognitive abilities"
            ]
            6 => array:2 [
              "identificador" => "sec0115"
              "titulo" => "Aversion to light"
            ]
            7 => array:2 [
              "identificador" => "sec0120"
              "titulo" => "Adaptation of the retina to light"
            ]
          ]
        ]
        11 => array:3 [
          "identificador" => "sec0125"
          "titulo" => "Contribution of intrinsically photosensitive retinal ganglion cells to visual image-forming functions"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0130"
              "titulo" => "The colour of light in circadian synchronisation"
            ]
          ]
        ]
        12 => array:2 [
          "identificador" => "sec0135"
          "titulo" => "Non-image-forming visual functions in the disease"
        ]
        13 => array:2 [
          "identificador" => "sec0140"
          "titulo" => "Visual functions of intrinsically photosensitive retinal ganglion cells in the postnatal period"
        ]
        14 => array:2 [
          "identificador" => "sec0145"
          "titulo" => "Melanopsin phototransduction"
        ]
        15 => array:2 [
          "identificador" => "sec0150"
          "titulo" => "Final considerations"
        ]
        16 => array:2 [
          "identificador" => "sec0155"
          "titulo" => "Funding"
        ]
        17 => array:2 [
          "identificador" => "sec0160"
          "titulo" => "Conflict of interest"
        ]
        18 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-05-21"
    "fechaAceptado" => "2020-06-15"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1379101"
          "palabras" => array:5 [
            0 => "Intrinsically photosensitive retinal ganglion cells"
            1 => "Melanopsin retinal ganglion cells"
            2 => "Retina"
            3 => "M1-M6 melanopsin cells"
            4 => "Non-image forming visual system"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1379100"
          "palabras" => array:5 [
            0 => "C&#233;lulas ganglionares intr&#237;nsecamente fotosensibles"
            1 => "C&#233;lulas ganglionares melanos&#237;nicas"
            2 => "Retina"
            3 => "C&#233;lulas M1-M6"
            4 => "Sistema visual no formador de im&#225;genes"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Our visual system has evolved to provide us with an image of the scene that surrounds us&#44; informing us of its texture&#44; colour&#44; movement&#44; and depth with an enormous spatial and temporal resolution&#44; and for this purpose&#44; the image formation &#40;IF&#41; dedicates the vast majority of our retinal ganglion cell &#40;RGC&#41; population and much of our cerebral cortex&#46; On the other hand&#44; a minuscule proportion of RGCs&#44; in addition to receiving information from classic cone and rod photoreceptors&#44; express melanopsin and are intrinsically photosensitive &#40;ipRGC&#41;&#46; These ipRGC are dedicated to non-image-forming &#40;NIF&#41; visual functions&#44; of which we are unaware&#44; but which are essential for aspects related to our daily physiology&#44; such as the timing of our circadian rhythms and our pupillary light reflex&#44; among many others&#46; Before the discovery of ipRGCs&#44; it was thought that the IF and NIF functions were distinct compartments regulated by different RGCs&#44; but this concept has evolved in recent years with the discovery of new types of ipRGCs that innervate subcortical IF regions&#44; and therefore have IF visual functions&#46; Six different types of ipRGCs are currently known&#46; These are termed M1-M6&#44; and differ in their morphological&#44; functional&#44; molecular properties&#44; central projections&#44; and visual behaviour responsibilities&#46; A review is presented on the melanopsin visual system&#44; the most active field of research in vision&#44; for which knowledge has grown exponentially during the last two decades&#44; when RGCs giving rise to this pathway were first discovered&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestro sistema visual ha evolucionado para proveernos una imagen de la escena que nos rodea inform&#225;ndonos de su textura&#44; color&#44; movimiento&#44; y profundidad con una enorme capacidad de resoluci&#243;n tanto espacial como temporal&#44; y a esta finalidad&#44; la formaci&#243;n de im&#225;genes &#40;FI&#41; dedica la inmensa mayor&#237;a de nuestras c&#233;lulas ganglionares de la retina &#40;CGR&#41; y gran parte de nuestra corteza cerebral&#46; Por otra parte&#44; una proporci&#243;n min&#250;scula de CGR&#44; adem&#225;s de recibir informaci&#243;n de fotorreceptores cl&#225;sicos conos y bastones&#44; expresan melanopsina y son intr&#237;nsecamente fotosensibles &#40;CGRif&#41;&#46; Estas CGRif se dedican a funciones visuales no formadoras de im&#225;genes &#40;NFI&#41;&#44; de las que somos inconscientes&#44; pero que resultan imprescindibles para aspectos relacionados con nuestra fisiolog&#237;a cotidiana como la puesta en hora de nuestros ritmos circadianos y nuestro reflejo fotomotor&#44; entre otras muchas&#46; Desde el descubrimiento de las CGRif se pens&#243; que las funciones FI y NFI eran compartimentos distintos regulados por diferentes CGR&#44; pero este concepto ha evolucionado en los &#250;ltimos a&#241;os con el descubrimiento de nuevos tipos de CGRif que inervan regiones subcorticales FI y por tanto presentan funciones FI&#46; Hoy se conocen 6 tipos diferentes de CGRif que se denominan M1-M6 y difieren en sus propiedades morfol&#243;gicas&#44; funcionales&#44; moleculares&#44; proyecciones centrales y responsabilidades en comportamientos visuales&#46; En este trabajo revisamos el sistema visual melanops&#237;nico&#44; el campo de investigaci&#243;n m&#225;s activo en visi&#243;n y cuyo conocimiento ha crecido exponencialmente durante las &#250;ltimas dos d&#233;cadas&#44; desde que se descubrieron por primera vez las CGR que dan origen a esta v&#237;a&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Vidal-Villegas B&#44; Gallego-Ortega A&#44; Miralles de Imperial-Ollero JA&#44; Mart&#237;nez de la Casa JM&#44; Garc&#237;a Feijoo J&#44; Vidal-Sanz M&#46; C&#233;lulas ganglionares fotosensibles&#58; una poblaci&#243;n diminuta pero esencial&#46; Arch Soc Esp Oftalmol&#46; 2021&#59;96&#58;299&#8211;315&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2487
            "Ancho" => 2925
            "Tamanyo" => 1377491
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A&#41; Photomontage of an adult rat retina showing intrinsically photosensitive retinal ganglion cells &#40;RGCif&#41; marked with melanopsin &#40;RGCm<span class="elsevierStyleSup">&#43;</span>&#41;&#44; distributed throughout the retina&#46; B&#41; Adjacency map of the same retina &#40;A&#41; that shows the topographic distribution of the RGCm<span class="elsevierStyleSup">&#43;</span>&#44; which were counted manually&#44; a total of 2&#44;683&#46; Colour scale of the adjacency map in which each colour represents an increase of 4 adjacents within a radius of 0&#46;22<span class="elsevierStyleHsp" style=""></span>mm and ranges from purple &#40;0-6 adjacents&#41; to dark red &#40;42-48 adjacents&#41;&#46; C and D&#41; Details with a greater increase in which the marking of the RGCif can be seen&#44; both in their cellular somas and in their extensive dendrites in the focus plane &#40;For interpretation of the references to colour in this figure legend&#44; the reader is referred to the web version of this article&#41;&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Bar&#58; A&#58;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm&#44; C&#58;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>&#956; m&#44; D<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25<span class="elsevierStyleHsp" style=""></span>&#956; m&#59; I&#58; lower&#59; N&#58; nasal&#59; S&#58; upper&#59; T&#58; temporary&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1768
            "Ancho" => 2925
            "Tamanyo" => 1044893
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A&#41; Photomontage of a pigmented mouse retina showing retinal ganglion cells marked with antibodies that recognise non-phosphorylated high molecular weight neurofilaments &#40;SMI32&#41; and calbindine&#46; The cells marked with SMI32 correspond to the RGC&#945; type&#44; while those doubly marked are marked with white dots and correspond to the intrinsically photosensitive M4 RGC type&#46; In this retina&#44; 580 M4 RGCif were counted&#46; Note the distribution of these cells on the nasal-temporal axis with a higher density in the super-temporal quadrant&#46; B-D&#41; Details at higher magnification showing the marking of the RGCifs &#945;with SMI32 &#40;B&#41;&#44; calbindine &#40;C&#41; and double marking of the RGCifs M4 &#40;D&#41;&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Bar&#58; A<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>&#956; m&#44; B&#8211;D<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>&#956; m&#59; I&#58; lower&#59; N&#58; nasal&#59; S&#58; upper&#59; T&#58; temporary&#46;</p>"
        ]
      ]
      2 => array:9 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Source&#58; Fernandez et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Duda et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Sondereker et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Delwig et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a> Gooley et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a> Li and Schmidt&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a> Do<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a> and Lucas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a>"
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The most important retinal cores of the non-image-forming NFI &#40;bold&#41; and image-forming FI &#40;italic&#41; visual functions are highlighted&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#91;Main RGCif innervation areas</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prosencephalon and hypothalamus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preoptic area &#40;ventrolateral&#44; lateral&#44; medial&#41;&#44; subparaventricular area&#44; <span class="elsevierStyleBold">suprachiasmatic nucleus&#44;</span> perisupraoptic nucleus&#44; anterior and lateral regions of the hypothalamus&#44; amygdala &#40;anterior&#44; medial and central&#41;&#44; nucleus of the terminal striae&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">THALAMUS and habenula&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Perihabenular nucleus&#44; <span class="elsevierStyleItalic">lateral dorsal geniculate&#44;</span> lateral ventral geniculate&#44; intergeniculate leaflet&#44; uncertain zone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Midbrain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Periaqueductal grey substance&#44; <span class="elsevierStyleBold">pretectal olive core&#44;</span> pretectal nuclei &#40;anterior&#44; medial and posterior&#41;&#44; nucleus of the optic tract&#44; <span class="elsevierStyleItalic">visual layers of the upper colliculus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Accessory optical system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dorsal&#44; lateral and medial terminal cores&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2614012.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Main innervation territories of intrinsically photosensitive retinal ganglion cells &#40;RGCif&#41; in mice&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:124 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:3 [
                        "editores" => "H&#46;Kolb, E&#46;Fernandez, R&#46;F&#46;Nelson"
                        "titulo" => "The Architecture of the Human Fovea"
                        "serieFecha" => "1995"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Central projections of melanopsin-expressing retinal ganglion cells in the mouse"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.20970"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Comp Neurol&#46;"
                        "fecha" => "2006"
                        "volumen" => "497"
                        "paginaInicial" => "326"
                        "paginaFinal" => "349"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Circadian physiology of metabolism"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.aah4967"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "2016"
                        "volumen" => "354"
                        "paginaInicial" => "1008"
                        "paginaFinal" => "1015"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Light Affects Mood and Learning through Distinct Retina-Brain Pathways"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2018.08.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell&#46;"
                        "fecha" => "2018"
                        "volumen" => "175"
                        "paginaInicial" => "71"
                        "paginaFinal" => "84"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Distinct ipRGC subpopulations mediate light&#8217;s acute and circadian effects on body temperature and sleep"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7554/eLife.44358"
                      "Revista" => array:4 [
                        "tituloSerie" => "Elife&#46;"
                        "fecha" => "2019"
                        "volumen" => "8"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.0808312105"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci&#46;"
                        "fecha" => "2008"
                        "volumen" => "105"
                        "paginaInicial" => "19998"
                        "paginaFinal" => "20003"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glutamatergic Neurotransmission from Melanopsin Retinal Ganglion Cells Is Required for Neonatal Photoaversion but Not Adult Pupillary Light Reflex"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0083974"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One&#46;"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "link" => array:1 [ …1]
                        "itemHostRev" => array:3 [ …3]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current understanding of photophobia&#44; visual networks and headaches"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0333102418784750"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cephalalgia&#46;"
                        "fecha" => "2019"
                        "volumen" => "39"
                        "paginaInicial" => "1623"
                        "paginaFinal" => "1634"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Architecture&#44; Function&#44; and Assembly of the Mouse Visual System"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1146/annurev-neuro-071714-033842"
                      "Revista" => array:6 [
                        "tituloSerie" => "Annu Rev Neurosci&#46;"
                        "fecha" => "2017"
                        "volumen" => "40"
                        "paginaInicial" => "499"
                        "paginaFinal" => "538"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin&#58; From a small molecule to brain functions"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neubiorev.2020.03.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurosci Biobehav Rev&#46;"
                        "fecha" => "2020"
                        "volumen" => "113"
                        "paginaInicial" => "190"
                        "paginaFinal" => "203"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Crosstalk&#58; The diversity of melanopsin ganglion cell types has begun to challenge the canonical divide between image&#8208;forming and non&#8208;image&#8208;forming vision"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.24873"
                      "Revista" => array:2 [
                        "tituloSerie" => "J Comp Neurol&#46;"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term effect of optic nerve axotomy on the retinal ganglion cell layer"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1167/iovs.15-17195"
                      "Revista" => array:5 [
                        "tituloSerie" => "Investig Ophthalmol Vis Sci&#46;"
                        "fecha" => "2015"
                        "volumen" => "56"
                        "paginaInicial" => "6095"
                        "paginaFinal" => "6112"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The functional diversity of retinal ganglion cells in the mouse"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature16468"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature&#46;"
                        "fecha" => "2016"
                        "volumen" => "529"
                        "paginaInicial" => "345"
                        "paginaFinal" => "350"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Parallel processing in the mammalian retina"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrn1497"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Neurosci&#46;"
                        "fecha" => "2004"
                        "volumen" => "5"
                        "paginaInicial" => "747"
                        "paginaFinal" => "757"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Retinofugal projections in the mouse"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.23635"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Comp Neurol&#46;"
                        "fecha" => "2014"
                        "volumen" => "522"
                        "paginaInicial" => "3733"
                        "paginaFinal" => "3753"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1067262"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "2002"
                        "volumen" => "295"
                        "paginaInicial" => "1070"
                        "paginaFinal" => "1073"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-Containing Retinal Ganglion Cells&#58; Architecture&#44; Projections&#44; and Intrinsic Photosensitivity"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1069609"
                      "Revista" => array:7 [
                        "tituloSerie" => "Science"
                        "fecha" => "2002"
                        "volumen" => "295"
                        "paginaInicial" => "1065"
                        "paginaFinal" => "1070"
                        "link" => array:1 [ …1]
                        "itemHostRev" => array:3 [ …3]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin&#58; An opsin in melanophores&#44; brain&#44; and eye"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.95.1.340"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci&#46;"
                        "fecha" => "1998"
                        "volumen" => "95"
                        "paginaInicial" => "340"
                        "paginaFinal" => "345"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A Novel Human Opsin in the Inner Retina"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.20-02-00600.2000"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Neurosci&#46;"
                        "fecha" => "2000"
                        "volumen" => "20"
                        "paginaInicial" => "600"
                        "paginaFinal" => "605"
                        "link" => array:1 [ …1]
                        "itemHostRev" => array:3 [ …3]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin Is Expressed in PACAP-Containing Retinal Ganglion Cells of the Human Retinohypothalamic Tract"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1167/iovs.04-0313"
                      "Revista" => array:5 [
                        "tituloSerie" => "Investig Opthalmology Vis Sci&#46;"
                        "fecha" => "2004"
                        "volumen" => "45"
                        "paginaInicial" => "4202"
                        "itemHostRev" => array:3 [ …3]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature03387"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature&#46;"
                        "fecha" => "2005"
                        "volumen" => "433"
                        "paginaInicial" => "749"
                        "paginaFinal" => "754"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PACAP and glutamate are co-stored in the retinohypothalamic tract"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Comp Neurol&#46;"
                        "fecha" => "2000"
                        "volumen" => "418"
                        "paginaInicial" => "147"
                        "paginaFinal" => "155"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1077293"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "2003"
                        "volumen" => "299"
                        "paginaInicial" => "245"
                        "paginaFinal" => "247"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin and rod&#8211;cone photoreceptive systems account for all major accessory visual functions in mice"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature01761"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nature&#46;"
                        "fecha" => "2003"
                        "volumen" => "424"
                        "paginaInicial" => "75"
                        "paginaFinal" => "81"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin cells are the principal conduits for rod&#8211;cone input to non-image-forming vision"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature06829"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature&#46;"
                        "fecha" => "2008"
                        "volumen" => "453"
                        "paginaInicial" => "102"
                        "paginaFinal" => "105"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inducible Ablation of Melanopsin-Expressing Retinal Ganglion Cells Reveals Their Central Role in Non-Image Forming Visual Responses"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0002451"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One&#46;"
                        "fecha" => "2008"
                        "volumen" => "3"
                        "paginaInicial" => "e2451"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Photopigment Melanopsin Is Exclusively Present in Pituitary Adenylate Cyclase-Activating Polypeptide-Containing Retinal Ganglion Cells of the Retinohypothalamic Tract"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.22-01-j0002.2002"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurosci&#46;"
                        "fecha" => "2002"
                        "volumen" => "22"
                        "paginaInicial" => "RC191"
                        "link" => array:1 [ …1]
                        "itemHostRev" => array:3 [ …3]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin Contributions to Irradiance Coding in the Thalamo-Cortical Visual System"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pbio.1000558"
                      "Revista" => array:4 [
                        "tituloSerie" => "PLoS Biol&#46;"
                        "fecha" => "2010"
                        "volumen" => "8"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-Expressing Retinal Ganglion-Cell Photoreceptors&#58; Cellular Diversity and Role in Pattern Vision"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neuron.2010.05.023"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuron&#46;"
                        "fecha" => "2010"
                        "volumen" => "67"
                        "paginaInicial" => "49"
                        "paginaFinal" => "60"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Form and Function of the M4 Cell&#44; an Intrinsically Photosensitive Retinal Ganglion Cell Type Contributing to Geniculocortical Vision"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.1422-12.2012"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurosci&#46;"
                        "fecha" => "2012"
                        "volumen" => "32"
                        "paginaInicial" => "13608"
                        "paginaFinal" => "13620"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A Role for Melanopsin in Alpha Retinal Ganglion Cells and Contrast Detection"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neuron.2014.03.022"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuron&#46;"
                        "fecha" => "2014"
                        "volumen" => "82"
                        "paginaInicial" => "781"
                        "paginaFinal" => "788"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The M5 Cell&#58; A Color-Opponent Intrinsically Photosensitive Retinal Ganglion Cell"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neuron.2017.11.030"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neuron&#46;"
                        "fecha" => "2018"
                        "volumen" => "97"
                        "paginaInicial" => "150"
                        "paginaFinal" => "163"
                        "link" => array:1 [ …1]
                        "itemHostRev" => array:3 [ …3]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The M6 cell&#58; A small-field bistratified photosensitive retinal ganglion cell"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.24556"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Comp Neurol&#46;"
                        "fecha" => "2019"
                        "volumen" => "527"
                        "paginaInicial" => "297"
                        "paginaFinal" => "311"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin Contributions to the Representation of Images in the Early Visual System"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cub.2017.04.046"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Biol&#46;"
                        "fecha" => "2017"
                        "volumen" => "27"
                        "paginaInicial" => "1623"
                        "paginaFinal" => "1632"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Form vision from melanopsin in humans"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41467-019-10113-3"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Commun&#46;"
                        "fecha" => "2019"
                        "volumen" => "10"
                        "paginaInicial" => "2274"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Morphology and mosaics of melanopsin-expressing retinal ganglion cell types in mice"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.22381"
                      "Revista" => array:4 [
                        "tituloSerie" => "J Comp Neurol&#46;"
                        "fecha" => "2010"
                        "volumen" => "518"
                        "paginaInicial" => "NA"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intrinsically photosensitive retinal ganglion cells&#58; many subtypes&#44; diverse functions"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.tins.2011.07.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Trends Neurosci&#46;"
                        "fecha" => "2011"
                        "volumen" => "34"
                        "paginaInicial" => "572"
                        "paginaFinal" => "580"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mood&#44; the Circadian System&#44; and Melanopsin Retinal Ganglion Cells"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1146/annurev-neuro-072116-031324"
                      "Revista" => array:6 [
                        "tituloSerie" => "Annu Rev Neurosci&#46;"
                        "fecha" => "2017"
                        "volumen" => "40"
                        "paginaInicial" => "539"
                        "paginaFinal" => "556"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transcriptomic Signatures of Postnatal and Adult Intrinsically Photosensitive Ganglion Cells"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/ENEURO.0022-19.2019"
                      "Revista" => array:4 [
                        "tituloSerie" => "Eneuro&#46;"
                        "fecha" => "2019"
                        "volumen" => "6"
                        "itemHostRev" => array:3 [ …3]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.22579"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Comp Neurol&#46;"
                         …5
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Displaced retinal ganglion cells in albino and pigmented rats"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fnana.2014.00099"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Retinal neurodegeneration in experimental glaucoma"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/bs.pbr.2015.04.008"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identifying specific RGC types may shed light on their idiosyncratic responses to neuroprotection"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4103/1673-5374.162751"
                      "Revista" => array:2 [ …2]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular Hypertension"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fnins.2017.00235"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin expression is an indicator of the well-being of melanopsin-expressing retinal ganglion cells but not of their viability"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4103/1673-5374.189182"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nerve fibre layer degeneration and retinal ganglion cell loss long term after optic nerve crush or transection in adult mice"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.exer.2018.02.010"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of Ocular Hypertension in the Visual System of Pigmented Mice"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0121134"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "BDNF rescues RGCs but not intrinsically photosensitive RGCs in ocular hypertensive albino rat retinas"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1167/iovs.15-16454"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin&#43;RGCs Are fully Resistant to NMDA-Induced Excitotoxicity"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/ijms20123012"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn3a"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1167/iovs.15-16808"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Light-induced retinal degeneration causes a transient downregulation of melanopsin in the rat retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.exer.2017.05.010"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-containing or non-melanopsin-containing retinal ganglion cells response to acute ocular hypertension with or without brain-derived neurotrophic factor neuroprotection"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1167/iovs.16-20146"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Whole Number&#44; Distribution and Co-Expression of Brn3 Transcription Factors in Retinal Ganglion Cells of Adult Albino and Pigmented Rats"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0049830"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Number and spatial distribution of intrinsically photosensitive retinal ganglion cells in the adult albino rat"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.exer.2012.12.010"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature10206"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7554/eLife.22861"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Distribution of melanopsin positive neurons in pigmented and albino mice&#58; evidence for melanopsin interneurons in the mouse retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fnana.2014.00131"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Light and Darkness Regulate Melanopsin in the Retinal Ganglion Cells of the Albino Wistar Rat"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1385/JMN:27:2:147"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin changes in neonatal albino rat independent of rods and cones"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/WNR.0b013e328010ff56"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differential expression of melanopsin mRNA and protein in Brown Norwegian rats"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.exer.2012.11.006"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differential Expression of Two Distinct Functional Isoforms of Melanopsin &#40;Opn4&#41; in the Mammalian Retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.2036-09.2009"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin expressing human retinal ganglion cells&#58; Subtypes&#44; distribution&#44; and intraretinal connectivity"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.24181"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin Phototransduction Is Repurposed by ipRGC Subtypes to Shape the Function of Distinct Visual Circuits"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neuron.2018.06.032"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Subtype-Specific Regeneration of Retinal Ganglion Cells following Axotomy&#58; Effects of Osteopontin and mTOR Signaling"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neuron.2015.02.017"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Light as a central modulator of circadian rhythms&#44; sleep and affect"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrn3743"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Retinofugal Projections from Melanopsin-Expressing Retinal Ganglion Cells Revealed by Intraocular Injections of Cre-Dependent Virus"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0149501"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A Broad Role for Melanopsin in Nonvisual Photoreception"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.23-18-07093.2003"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Divergent projection patterns of M1 ipRGC subtypes"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.24469"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin and the Intrinsically Photosensitive Retinal Ganglion Cells&#58; Biophysics to Behavior"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neuron.2019.07.016"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Can We See with Melanopsin&#63;"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [ …3]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin ganglion cell outer retinal dendrites&#58; Morphologically distinct and asymmetrically distributed in the mouse retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.24293"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.celrep.2018.04.086"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recurrent axon collaterals of intrinsically photosensitive retinal ganglion cells"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1017/S0952523813000199"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "M1 ipRGCs Influence Visual Function through Retrograde Signaling in the Retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.3500-15.2016"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Architecture of retinal projections to the central circadian pacemaker"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.1523629113"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1113/jphysiol.2013.262782"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Overlapping morphological and functional properties between M4 and M5 intrinsically photosensitive retinal ganglion cells"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.24806"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Roles of Rods&#44; Cones&#44; and Melanopsin in Photoresponses of M4 Intrinsically Photosensitive Retinal Ganglion Cells &#40;ipRGCs&#41; and Optokinetic Visual Behavior"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fncel.2018.00203"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Four alpha ganglion cell types in mouse retina&#58; Function&#44; structure&#44; and molecular signatures"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0180091"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Colour As a Signal for Entraining the Mammalian Circadian Clock"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pbio.1002127"
                      "Revista" => array:3 [ …3]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-expressing ganglion cells on macaque and human retinas form two morphologically distinct populations"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.23995"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-expressing retinal ganglion cells in aging and disease"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.14670/HH-18-138"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/brain/awq155"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Photosensitive melanopsin-containing retinal ganglion cells in health and disease&#58; implications for circadian rhythms"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/ijms20133164"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A color vision circuit for non-image-forming vision in the primate retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cub.2020.01.040"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cne.23588"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0003153"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical implications of the melanopsin-based non&#8211;image-forming visual system"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000003761"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            88 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "89"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypomorphic Expression of Pitx3 Disrupts Circadian Clocks and Prevents Metabolic Entrainment of Energy Expenditure"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.celrep.2019.11.027"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            89 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "90"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Local photic entrainment of the retinal circadian oscillator in the absence of rods&#44; cones&#44; and melanopsin"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.1323350111"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            90 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "91"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The post-illumination pupil response is reduced in glaucoma patients"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1167/iovs.10-6023"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            91 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "92"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Measuring and using light in the melanopsin age"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.tins.2013.10.004"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            92 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "93"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Binocular summation in postillumination pupil response driven by melanopsin-containing retinal ganglion cells"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1167/iovs.18-24639"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            93 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "94"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Additive contributions of melanopsin and both cone types provide broadband sensitivity to mouse pupil control"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12915-018-0552-1"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            94 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "95"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The acute light-induction of sleep is mediated by OPN4-based photoreception"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nn.2179"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            95 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "96"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Type I intrinsically photosensitive retinal ganglion cells of early post-natal development correspond to the M4 subtype"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13064-015-0042-x"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            96 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "97"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dissecting a Role for Melanopsin in Behavioural Light Aversion Reveals a Response Independent of Conventional Photoreception"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0015009"
                      "Revista" => array:4 [ …4]
                    ]
                  ]
                ]
              ]
            ]
            97 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "98"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-dependent light avoidance in neonatal mice"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.1008533107"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            98 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "99"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Response of the infant rat to light prior to eyelid opening&#58; Mediation by the superior colliculus"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/dev.420110510"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            99 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "100"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of melanopsin-based irradiance detecting circuitry"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1749-8104-6-8"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            100 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "101"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cub.2007.04.058"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            101 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "102"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Retinal dopamine mediates multiple dimensions of light-adapted vision"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.0711-12.2012"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            102 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "103"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Behavioral assessment of visual acuity in mice and rats"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0042-6989(00)00081-X"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            103 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "104"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-driven increases in maintained activity enhance thalamic visual response reliability across a simulated dawn"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.1505274112"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            104 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "105"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A Colourful Clock"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pbio.1002160"
                      "Revista" => array:3 [ …3]
                    ]
                  ]
                ]
              ]
            ]
            105 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "106"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chromatic clocks&#58; Color opponency in non-image-forming visual function"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neubiorev.2017.04.016"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            106 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "107"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Degeneration of human photosensitive retinal ganglion cells may explain sleep and circadian rhythms disorders in Parkinson&#8217;s disease"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s40478-018-0596-z"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            107 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "108"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Loss of melanopsin-expressing ganglion cell subtypes and dendritic degeneration in the aging human retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fnagi.2017.00079"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            108 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "109"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin retinal ganglion cell loss in Alzheimer disease"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ana.24548"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            109 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "110"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ophtha.2018.01.036"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            110 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "111"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Circadian Rhythm Disorders and Melatonin Production in 127 Blind Women with and without Light Perception"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0748730414536852"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            111 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "112"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Physiologic Diversity and Development of Intrinsically Photosensitive Retinal Ganglion Cells"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neuron.2005.09.031"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            112 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "113"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cellular properties of intrinsically photosensitive retinal ganglion cells during postnatal development"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13064-019-0132-2"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            113 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "114"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin-Dependent Photoreception Provides Earliest Light Detection in the Mammalian Retina"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cub.2005.05.053"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            114 => array:3 [
              "identificador" => "bib0575"
              "etiqueta" => "115"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A direct and melanopsin-dependent fetal light response regulates mouse eye development"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature11823"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            115 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "116"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intrinsically photosensitive ganglion cells contribute to plasticity in retinal wave circuits"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.1222150110"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            116 => array:3 [
              "identificador" => "bib0585"
              "etiqueta" => "117"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Light acts through melanopsin to alter retinal waves and segregation of retinogeniculate afferents"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nn.2845"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            117 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "118"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin ganglion cells use a membrane-associated rhabdomeric phototransduction cascade"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/jn.01066.2007"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            118 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "119"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characterisation of light responses in the retina of mice lacking principle components of rod&#44; cone and melanopsin phototransduction signalling pathways"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/srep28086"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            119 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "120"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Melanopsin phototransduction&#58; great excitement over a poor catch"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cub.2009.01.034"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            120 => array:3 [
              "identificador" => "bib0605"
              "etiqueta" => "121"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "M1 intrinsically photosensitive retinal ganglion cells integrate rod and melanopsin inputs to signal in low light"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.celrep.2019.11.024"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            121 => array:3 [
              "identificador" => "bib0610"
              "etiqueta" => "122"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A retinal ganglion cell that can signal irradiance continuously for 10 hours"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.1423-12.2012"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            122 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "123"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chromophore regeneration&#58; Melanopsin does its own thing"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.0603955103"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            123 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "124"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Structural basis for ON-and OFF-center responses in retinal ganglion cells"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.959847"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21735794/0000009600000006/v1_202106040601/S2173579420302401/v1_202106040601/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "5815"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735794/0000009600000006/v1_202106040601/S2173579420302401/v1_202106040601/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420302401?idApp=UINPBA00004N"
]