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array:24 [ "pii" => "S217357942030013X" "issn" => "21735794" "doi" => "10.1016/j.oftale.2019.11.004" "estado" => "S300" "fechaPublicacion" => "2020-02-01" "aid" => "1607" "copyright" => "Sociedad Española de Oftalmología" "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Soc Esp Oftalmol. 2020;95:84-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0365669119303624" "issn" => "03656691" "doi" => "10.1016/j.oftal.2019.11.013" "estado" => "S300" "fechaPublicacion" => "2020-02-01" "aid" => "1607" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Soc Esp Oftalmol. 2020;95:84-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 15 "formatos" => array:2 [ "HTML" => 9 "PDF" => 6 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Comunicación corta</span>" "titulo" => "El receptor de dopamina D2 influye en el desarrollo y la función del ojo en el pez cebra" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "84" "paginaFinal" => "89" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Dopamine D2 receptor influences eye development and function in Zebrafish" ] ] "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" => "fig0020" "etiqueta" => "Figura 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1025 "Ancho" => 2508 "Tamanyo" => 217126 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Inmunomarcaje doble para TH y AcTub en la retina de peces cebra adultos. TH se colocaliza con AcTub en las células amacrinas (indicado por flechas). El marcaje de Actub muestra tinción positiva en células ganglionares, amacrinas y en fibras del IPL e INL. Barra de escala: 10<span class="elsevierStyleHsp" style=""></span>μm. GCL: capa de células ganglionares; INL: capa nuclear interna; IPL: capa plexiforme interna.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Z. Syambani Ulhaq" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Z." "apellidos" => "Syambani Ulhaq" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S217357942030013X" "doi" => "10.1016/j.oftale.2019.11.004" "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/S217357942030013X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669119303624?idApp=UINPBA00004N" "url" => "/03656691/0000009500000002/v2_202108160545/S0365669119303624/v2_202108160545/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173579420300037" "issn" => "21735794" "doi" => "10.1016/j.oftale.2019.11.002" "estado" => "S300" "fechaPublicacion" => "2020-02-01" "aid" => "1590" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Soc Esp Oftalmol. 2020;95:90-3" "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" => "Management of the neovascular choroidal membrane secondary to ocular toxoplasmosis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "90" "paginaFinal" => "93" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Manejo de la membrana neovascular coroidea secundaria a toxoplasmosis ocular" ] ] "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" => 704 "Ancho" => 1405 "Tamanyo" => 132304 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0095" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Active chorioretinitis locus (asterisk) adjacent to a macular scar and an intraretinal hemorrhage in the LE (arrow). CNVM existence was confirmed by means of macular OCT.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "E. Martín García, J.J. Chávarri García, L. Rodríguez Vicente, B. Jiménez del Río, S.M. Guallar Leza, J.L. del Río Mayor" "autores" => array:6 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Martín García" ] 1 => array:2 [ "nombre" => "J.J." "apellidos" => "Chávarri García" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Rodríguez Vicente" ] 3 => array:2 [ "nombre" => "B." "apellidos" => "Jiménez del Río" ] 4 => array:2 [ "nombre" => "S.M." "apellidos" => "Guallar Leza" ] 5 => array:2 [ "nombre" => "J.L." "apellidos" => "del Río Mayor" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669119303260" "doi" => "10.1016/j.oftal.2019.11.003" "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/S0365669119303260?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420300037?idApp=UINPBA00004N" "url" => "/21735794/0000009500000002/v1_202002061534/S2173579420300037/v1_202002061534/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2173579420300013" "issn" => "21735794" "doi" => "10.1016/j.oftale.2019.09.013" "estado" => "S300" "fechaPublicacion" => "2020-02-01" "aid" => "1574" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Arch Soc Esp Oftalmol. 2020;95:75-83" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "New therapeutic targets in the treatment of age-related macular degeneration" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "75" "paginaFinal" => "83" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nuevas dianas terapéuticas en el tratamiento de la degeneración macular asociada a la edad" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P.V. Muñoz-Ramón, P. Hernández Martínez, F.J. Muñoz-Negrete" "autores" => array:3 [ 0 => array:2 [ "nombre" => "P.V." "apellidos" => "Muñoz-Ramón" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Hernández Martínez" ] 2 => array:2 [ "nombre" => "F.J." "apellidos" => "Muñoz-Negrete" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579420300013?idApp=UINPBA00004N" "url" => "/21735794/0000009500000002/v1_202002061534/S2173579420300013/v1_202002061534/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Short communication</span>" "titulo" => "Dopamine D2 receptor influences eye development and function in Zebrafish" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "84" "paginaFinal" => "89" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Z. Syambani Ulhaq" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Z." "apellidos" => "Syambani Ulhaq" "email" => array:1 [ 0 => "zulhaq@kedokteran.uin-malang.ac.id" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Biomedical Science, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim Islamic State University, Batu, East Java, Indonesia" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El receptor de dopamina D2 influye en el desarrollo y la función del ojo en el pez cebra" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1025 "Ancho" => 2508 "Tamanyo" => 217498 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Double immunostaining for TH and AcTub in the adult zebrafish retina. TH was co-localized with AcTub in the amacrine cell (indicated by arrow). AcTub staining shows positive staining in ganglion cells, amacrine cells, and in the fibers of the IPL and INL. Scale bar: 10 μm. GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Zebrafish is an emerging model species for evaluating the vertebrate visual system because it closely resembles a human eye.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Dopamine is a neurotransmitter synthesized from the <span class="elsevierStyleSmallCaps">l</span>-amino acid tyrosine by a rate-limiting enzyme TH.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Although dopaminergic (DA) neurons play a role in various brain functions,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> dopamine is also considered as a major catecholamine presence in the vertebrate retina,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> thereby suggesting a tropic role of dopamine for retinal function. In zebrafish,TH anddopamine transporter are detected in amacrine cells as early as 2.5 days post-fertilization (dpf),<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> while the dopamine D1 receptor (DRD1) is detected in the inner retina, dopamine D2/D3 receptor (DRD2/DRD3) are localized in the inner nuclear layer (INL) and retinal ganglion cell (RGC) at 5-dpf.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> It has been reported that dopamine signaling pathways are mainly mediated by D1 and D2 receptors.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However, the absence of DRD2 seems to have a little role in retinal physiology.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Therefore, in this present study, the possible role of DRD2 in modulating eye development and function in zebrafish was evaluated by exposing the embryos with DRD2 agonist and/or antagonist and then parameters such as the eye size, optic nerve diameter, and visual background adaptation were examined.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Fish maintenance and embryo culture</span><p id="par0010" class="elsevierStylePara elsevierViewall">Adult zebrafish (<span class="elsevierStyleItalic">Danio rerio</span>) purchased from a local pet store were raised in a 60-L tank at 26–30 °C under the 14 h dark/10 h light cycle. Fertilized eggs were rinsed in embryo medium (EM) (0.004 % CaCl<span class="elsevierStyleInf">2</span>, 0.163 % MgSO<span class="elsevierStyleInf">4</span>, 0.1 % NaCl and 0.003 % KCl) and cultured in a 6-well plate (30 eggs/8 mL EM/well) at 28 ± 0.5 °C. All experimental procedures and maintenance of fish were conducted under the Guide for Care and Use of Laboratory Animals published by the US National Institutes of Health.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Exposure experiment</span><p id="par0015" class="elsevierStylePara elsevierViewall">Stock solutions of fluphenazine hydrochloride (Fph, DRD2 antagonist) (Sigma-Aldrich) at 100 mM and quinpirole hydrochloride (Qui, DRD2 agonist) (Sigma-Aldrich) at 200 mM were prepared in dimethyl sulfoxide (DMSO) and distilled water, respectively. For exposure experiments, stock solutions were then diluted in EM to the final concentrations at 100 μM and 200 μM for Fph and Qui, respectively. Control embryos were cultured in 0.1 % DMSO. Exposure started at 2 h post-fertilization (hpf) and continued till embryos and larvae were subjected to the assays. The media were changed daily.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Eye size and body length measurement</span><p id="par0020" class="elsevierStylePara elsevierViewall">Embryos at 2 or 5-dpf were anesthetized with 0.016 % MS-222 (Sigma-Aldrich), mounted in 0.5 % agarose (Bio-Rad), and the longest axis of a dorsal view of an eye and the body length in lateral position were measured under the stereomicroscope (Leica 58APO). Ten embryos per group were examined, and the experiments were repeated three times with eggs collected from different spawns.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Immunohistochemistry</span><p id="par0025" class="elsevierStylePara elsevierViewall">For whole-mount immunohistochemistry, the acetylated tubulin antibody was used to label RGC axons. 2-dpf embryos were fixed in 4 % PFA, and pigment was removed by incubation in 3 % H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span>/1 % KOH. The embryos were incubated with the mouse anti-acetylated tubulin (1:1000, Sigma-Aldrich) followed by incubation with Alexa Fluor 488 goat anti-mouse IgG (1:100, Invitrogen), and then observed under the fluorescence microscope (Leica MI65 FC). ImageJ was used to measure the diameter of the optic nerve observed from the ventral position. Ten embryos per group were examined, and the experiments were repeated three times with eggs collected from different spawns. Only 2-dpf embryos were used for this experiment because the antibody failed to penetrate at a later stage (5-dpf).</p><p id="par0030" class="elsevierStylePara elsevierViewall">For double staining immunohistochemistry, adult eyes were fixed in 4 % PFA, embedded in paraffin, and sectioned at 6 μm thickness. Deparaffinized slides were blocked and the slides were then subjected to antibody staining with primary antibodies for mouse anti-acetylated tubulin (AcTub, 1:500, Sigma-Aldrich) and rabbit anti-TH (1:500, Abcam) followed by incubation with Alexa Fluor 488 goat anti-mouse IgG (Invitrogen) and Alexa Flour 594 goat anti-rabbit IgG (Invitrogen) at 1:1000 dilution. Sections were mounted in Vectashield medium (Vector Laboratories) 4,6-diamino-2-phenylindole (DAPI) to visualize cell nuclei and observed under the fluorescence microscope Olympus BX53.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Visual background adaptation</span><p id="par0035" class="elsevierStylePara elsevierViewall">Visual background adaptation (VBA) was performed as previously described.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a> Briefly, 5-dpf larvae placed in a culture plate were incubated at 28.5 ℃ for 30 min in the dark, and then the images were taken under a stereomicroscope (Leica 58APO). The images were taken again after 15 min under the light. VBA assay was conducted with ten larvae per group, and the experiments were repeated three times with eggs collected from different spawns.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Statistical differences between groups were evaluated by one-way ANOVA followed by the least significant difference using StatPlus (a statistical program for Mac). Significant differences were accepted when <span class="elsevierStyleItalic">p</span> < 0.05.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">Fish exposed to Fph (DRD2 antagonist) and Qui (DRD2 agonist) were analyzed for alterations in eye size (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). 100 μM Fph significantly decreased eye diameter and delayed the eye development, both at 2 and 5-dpf, which were reversed by the addition of 200 μM Qui (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). 100 μM Fph significantly decreased eye/body length ratio at 2 and 5-dpf compared to control, co-incubation with 200 μM Qui reversed the effects caused by Fph (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). No significant changes in eye diameter and eye/body length ratio were observed in a lower dose of Fph and Qui exposed groups (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B, C).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Diameter of the optic nerve was evaluated using AcTub staining (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). 100 μM Fph significantly decreased optic nerve diameter compared to control, which was reversed by the addition of 200 μM Qui (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A, B). RGC axons were normally routed to the brain in all exposed groups. However, low-intensity staining in the ganglion cell layer (GCL) was observed when fish were exposed to 100 μM Fph (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). The eye function was evaluated with VBA (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A). 100 μM Fph significantly decreased VBA response compared to control, and the addition of 200 μM Qui reversed the effect caused by Fph (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>B). No significant changes either on the diameter of the optic nerve or VBA responses when fish were exposed to the lower dose of Fph and Qui (<a class="elsevierStyleCrossRef" href="#fig0010">Figs. 2</a>A, B; <a class="elsevierStyleCrossRef" href="#fig0015">3</a>A, B). Co-localization of TH with AcTub in adult zebrafish retina indicated that dopamine neurons were located in amacrine cells (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Expressions of AcTub were observed in subpopulations of ganglion cells, amacrine cells, and fibers in the inner plexiform layer (IPL) and inner nuclear layer (INL) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">This study demonstrated that DRD2 is essential for normal eye development and function in zebrafish. The decreased of eye size and developmental delays were only observed when fish were exposed to 100 μM Fph (DRD2 antagonist), which were then rescued by the addition of 200 μM Qui (DRD2 agonist). A reduction of the eye to the body length ratio was observed when fish were exposed to Fph, implying that eye development was specifically affected by DRD2. Previously, it has been shown that Fph had a great affinity to bind to DRD2.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Moreover, DRD2 is highly expressed in retinal DA neurons, particularly in INL and GCL.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,13,14</span></a> Thus, suggesting that DRD2 was likely modulating normal eye development through DA signaling pathway within the retina, although the mechanisms remain unclear. Nonetheless, a further examination in which retinal layer is affected by DRD2 signaling needs to be verified.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Because visual information is relayed on the intact optic nerve, AcTub staining was assessed to investigate the role of DRD2 on RGC axons. The data showed that Fph exposed fish had a hypoplastic optic nerve and low-intensity staining of ActTub located in the GCL, these possibly due to a reduction of RGC number and inhibition of RGC axonal growth. It has been shown the ablation of DRD2 decreased neurite growth. In addition, the administration of DRD2 agonist quinpirole stimulates neurite growth, which was reversed by the addition of dopamine antagonist haloperidol.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> These indicate that DRD2 plays a critical role in neural development. Visual function in zebrafish was evaluated with VBA assay. Background adaptation in teleost fish is mediated by ocular photoreception, thus aggregation of melanophore is observed when larvae are exposed to light.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In parallel with a small eye and a reduction of optic nerve diameter, melanophore behavior in embryos exposed to 100 μM Fph failed to respond to light, indicating the eye function was disrupted which were likely due to blockade of DRD2. In fact, mice lacking the DRD2 gene exhibited low b-wave signals.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Study shows depletion of dopamine reduces contrast sensitivity in TH knockout (KO) mice.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Furthermore, the administration of DRD2/3 antagonists decreased light sensitivity in rat RGCs.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Together, these support the evidence that dopamine is necessary for light-adapted vision. In conclusion, this present study showed that DRD2 plays an important role in eye development and function during early development of zebrafish. Considering the role of dopaminergic neurons in retinal development and function, it is possible to hypothesize that the dysfunction of dopaminergic neuron signaling pathways in the retina may cause visual abnormalities, particularly in the interactions between DA amacrine cells and photosensitive RGCs in modulating the light response.</p></span><span id="sec0051" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0071">Conflict of interests</span><p id="par0056" class="elsevierStylePara elsevierViewall">The author declares that he has no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1300360" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1199741" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1300361" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1199740" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Fish maintenance and embryo culture" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Exposure experiment" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Eye size and body length measurement" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Immunohistochemistry" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Visual background adaptation" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0051" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-09-19" "fechaAceptado" => "2019-11-26" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1199741" "palabras" => array:3 [ 0 => "Dopamine D2 receptor" 1 => "Eye development and function" 2 => "Zebrafish" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1199740" "palabras" => array:3 [ 0 => "Receptor de dopamina D2" 1 => "Desarrollo y función del ojo" 2 => "Pez cebra" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Dopamine is synthesized by tyrosine hydroxylase (TH) and is considered as a major catecholamine in the vertebrate retina, including zebrafish. Howeverlittle is known about the role of dopamine D2 receptor (DRD2) in retinal physiology. Therefore, to elucidate the role of DRD2 in the eye development and function in zebrafish, fish were exposed to fluphenazine (Fph), quinpirole (Qui), or combination of both. Subsequently, the eye size, optic nerve diameter (ONd), and visual background adaptation (VBA) were evaluated. The results showed that Fluphenazine (Fph, DRD2 antagonist) decreased eye size and optic nerve diameter followed by disruption of visual function. The addition of Quinpirole (Qui, DRD2 agonist) reversed the effects caused by Fph, implying that DRD2 is necessary for normal eye development and function in zebrafish. Considering the role of dopaminergic neurons in retinal development and function, dysfunction of dopaminergic neuron signaling pathways in the retina may cause visual abnormalities, particularly in the involvement of dopamine in regulating light response.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La dopamina es sintetizada por la tirosina hidroxilasa y es considerada como una catecola-mina mayor en la retina de los vertebrados, incluyendo el pez cebra. Sin embargo, se conoce poco sobre la función del receptor de dopamina D2 (DRD2) en la fisiología retiniana. Por lo tanto, para dilucidar el papel del DRD2 en el desarrollo y la función de los ojos en el pez cebra, los peces fueron expuestos a la flufenazina, quinpirol, o la combinación de ambos, y luego se evaluó el tamaño del ojo, el diámetro del nervio óptico (ONd) y la adaptación visual al fondo. Los resultados mostraron que la flufenazina (flufenazina, antagonista DRD2) disminuyó el tamaño del ojo y el diámetro del nervio óptico seguido de una interrupción de la función visual. La adición de quinpirol (quinpirol, agonista DRD2) invirtió los efectos causados por flufenazina, lo que implica que DRD2 es necesario para el desarrollo y la función normal del ojo en el pez cebra. Considerando el papel de las neuronas dopaminérgicas en el desarrollo y la función de la retina, la disfunción de las vías de señalización de las neuronas dopaminérgicas en la retina puede causar anormalidades visuales, particularmente en la participación de la dopamina en la regulación de la respuesta de la luz.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Syambani Ulhaq Z. El receptor de dopamina D2 influye en el desarrollo y la función del ojo en el pez cebra. Arch Soc Esp Oftalmol. 2020;95:84–89.</p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1071 "Ancho" => 3175 "Tamanyo" => 264291 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Effect of DRD2 antagonist (Fph) and DRD2 agonist (Qui) on eye size. (A) Representative images of the lateral view of fish exposed by Fph and Qui. (B) Changes in eye size of 2 and 5-dpf fish exposed to Fph and Qui. (C) Changes in the eye/body length ratio of 2 and 5-dpf fish exposed to Fph and Qui. Data are expressed as a mean ± standard error, n = 10 fish. (*) and (#) indicates a significant difference compared to control and between two groups indicated in the graphs (<span class="elsevierStyleItalic">p</span> < 0.05), respectively.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1251 "Ancho" => 2175 "Tamanyo" => 227302 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Effect of DRD2 antagonist (Fph) and DRD2 agonist (Qui) on optic nerve diameter. (A) Representative images of the ventral view of fish stained with acetylated tubulin for evaluation of optic nerve diameter. Insets show higher magnification at which arrows point; arrows indicate the location to measure the optic nerve diameter; arrowheads indicate ganglion cell layer; asterisks indicate optic chiasm. (B) Changes in optic nerve diameter of 2-dpf zebrafish embryos exposed to Fph and Qui. Data are expressed as a mean ± standard error, n = 10 fish. (*) indicates a significant difference compared to control (<span class="elsevierStyleItalic">p</span> < 0.05).</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1283 "Ancho" => 2508 "Tamanyo" => 287385 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Effect of DRD2 antagonist (Fph) and DRD2 agonist (Qui) on visual background adaptation. (A) The left panel shows a dorsal view of a 5-dpf larva, and the area in a white rectangle was used to evaluate melanophore behavior in VBA assay. Representative images of VBA assays in control and Fph exposed fish. (B) Changes in numbers of fish exhibited a positive response to light when fish were exposed to Fph and Qui. Data are expressed as a mean ± standard error, n = 10 fish. (*) indicates a significant difference compared to control (<span class="elsevierStyleItalic">p</span> < 0.05).</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1025 "Ancho" => 2508 "Tamanyo" => 217498 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Double immunostaining for TH and AcTub in the adult zebrafish retina. TH was co-localized with AcTub in the amacrine cell (indicated by arrow). AcTub staining shows positive staining in ganglion cells, amacrine cells, and in the fibers of the IPL and INL. Scale bar: 10 μm. GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:18 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zebrafish-on the move towards ophthalmological research" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:1 [ 0 => "J. 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