Hiperautofluorescencia foveal como factor predictor de recuperación visual en pacientes con desprendimiento regmatógeno de retina

Introducción: una de las causas de pobre ganancia visual luego de un tratamiento exitoso de desprendimiento de retina, sin complicaciones, es el daño de los fotoreceptores, reflejada en una disrupción de la capa de la zona elipsoide y membrana limitante externa (MLE). En otras patologías se ha demostrado que la hiperautofluorescencia foveal se correlaciona con la integridad de la zona elipsoide y MLE y una mejor recuperación visual. Objetivos: evaluar la asociación entre la hiperautofluorescencia foveal, la integridad de la capa de la zona elipsoide y recuperación visual luego de desprendimiento de retina regmatógeno (DRR) exitosamente tratado. Evaluar la concordancia inter-evaluador de estos exámenes. Metodología: estudio de corte transversal de autofluorescencia foveal y tomografía óptica coherente macular de dominio espectral en 65 pacientes con DRR evaluados por 3 evaluadores independientes. La concordancia inter-evaluador se estudio mediante Kappa de Cohen y la asociación entre las diferentes variables mediante la prueba chi cuadrado y pruebas Z para comparación de proporciones. Resultados: La concordancia de la autofluorescencia fue razonable y la de la tomografía óptica coherente macular buena a muy buena. Sujetos que presentaron hiperautofluorescencia foveal asociada a integridad de la capa de la zona elipsoide tuvieron 20% más de posibilidad de recuperar agudeza visual final mejor a 20/50 que los que no cumplieron éstas características. Conclusión: Existe una asociación clínicamente importante entre la hiperautofluorescencia foveal, la integridad de la capa de zona elipsoide y la mejor agudeza visual final, sin embargo ésta no fue estadísticamente significativa (p=0.39)

TRPV1 receptors modulate retinal development

We investigated the possible participation of TRPV1 channels in retinal apoptosis and overall development. Retinas from newborn, male albino rats were treated in vitro with capsazepine, a TRPV1 antagonist. The expression of cell cycle markers was not changed after TRPV1 blockade, whereas capsazepine reduced the number of apoptotic cells throughout the retina,increased ERK1/2 and p38 phosphorylation and slightly reduced JNK phosphorylation. The expression of BAD, Bcl-2, as well as integral and cleaved capsase-3 were similar in all experimental conditions. Newborn rats were kept for 2 months after receiving high doses of capsazepine. In their retinas, calbindin and parvalbumin protein levels were upregulated, but only the number of amacrine-like, parvalbumin-positive cells was increased. The numbers of calretinin, calbindin, ChAT, vimentin, PKC-alpha and GABA-positive cells were similar in both conditions. Protein expression of synapsin Ib was also increased in the retinas of capsazepine-treated rats. Calretinin, vimentin, GFAP, synapsin Ia, synaptophysin and light neurofilament protein levels were not changed when compared to control values. Our results indicate that TRPV1 channels play a role in the control of the early apoptosis that occur during retinal development, which might be dependent on MAPK signaling. Moreover, it seems that TRPV1 function might be important for neuronal and synaptic maturation in the retina. (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Connexin36, an Essential Element in the Rod Pathway, Is Highly Expressed in the Essentially Rodless Retina of Gallus gallus

Electrical coupling provided by connexins (Cx) in gap junctions (GJ) plays important roles in both the developing and the mature retina. In mammalian nocturnal species, Cx36 is an essential component in the rod pathway, the retinal circuit specialized for night, scotopic vision. Here, we report the expression of Cx36 in a species (Gallus gallus) that phylogenetic development endows with an essentially rodless retina. Cx36 gene is very highly expressed in comparison with other Cxs previously described in the adult retina, such as Cx43, Cx45, and Cx50. Moreover, real-time PCR, Western blot, and immunofluorescence all revealed that Cx36 expression massively increased over time during development. We thoroughly examined Cx36 in the inner and outer plexiform layers, where this protein was particularly abundant. Cx36 was observed mainly in the off sublamina of the inner plexiform layer rather than in the on sublamina previously described in the mammalian retina. In addition, Cx36 colocalized with specific cell markers, revealing the expression of this protein in distinct amacrine cells. To investigate further the involvement of Cx36 in visual processing, we examined its functional regulation in retinas from dark-adapted animals. Light deprivation markedly up-regulates Cx36 gene expression in the retina, resulting in an increased accumulation of the protein within and between cone synaptic terminals. In summary, the developmental regulation of Cx36 expression results in particular circuitry-related roles in the chick retina. Moreover, this study demonstrated that Cx36 onto- and phylogenesis in the vertebrate retina simultaneously exhibit similarities and particularities. J. Comp. Neurol. 512:651-663, 2009. (C) 2008 Wiley-Liss, Inc.

Lack of photoreceptor signaling alters the expression of specific synaptic proteins in the retina

Synaptic modulation by activity-dependent changes constitutes a cellular mechanism for neuronal plasticity. However, it is not clear how the complete lack of neuronal signaling specifically affects elements involved in the communication between neurons. In the retina, it is now well established that both chemical and electrical synapses are essential to mediate the transmission of visual signaling triggered by the photoreceptors. In this study, we compared the expression of synaptic proteins in the retinas of wild-type (WT) vs. rd/rd mice, an animal model that displays inherited and specific ablation of photoreceptors caused by a mutation in the gene encoding the beta-subunit of rod cGMP-phosphodiesterase (Pde6b(rd1)). We specifically examined the expression of connexins (Cx), the proteins that form the gap junction channels of electrical synapses, in addition to synaptophysin and synapsin 1, which are involved in the release of neurotransmitters at chemical synapses. Our results revealed that Cx36 gene expression levels are lower in the retinas of rd/rd when compared with WT. Confocal analysis indicated that Cx36 immunolabeling almost disappeared in the outer plexiform layer without significant changes in protein distribution within the inner plexiform layer of rd/rd retinas. Likewise, synaptophysin expression remarkably decreased in the outer plexiform layer of rd/rd retinas, and this down-regulation was also associated with diminished transcript levels. Furthermore, we observed down-regulation of Cx57 gene expression in rd/rd retinas when compared with WT and also changes in protein distribution. Interestingly, Cx45 and synapsin I expression in rd/rd retinas showed no noticeable changes when compared with WT. Taken together, our results revealed that the loss of photoreceptors leads to decreased expression of some synaptic proteins. More importantly, this study provides evidence that neuronal activity regulates, but is not essential to maintain, the expression of synaptic elements. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

TRPV1 receptors are involved in protein nitration and Muller cell reaction in the acutely axotomized rat retina

We report here the protein expression of TRPV1 receptor in axotomized rat retinas and its possible participation in mechanisms involved in retinal ganglion cell (RGC) death. Adult rats were subjected to unilateral, intraorbital axotomy of the optic nerve, and the retinal tissue was removed for further processing. TRPV1 total protein expression decreased progressively after optic nerve transection, reaching 66.2% of control values 21 days after axotomy. The number of cells labeled for TRPV1 in the remnant GCL decreased after 21 days post-lesion (to 63%). Fluoro-jade B staining demonstrated that the activation of TRPV1 in acutely-lesioned eyes elicited more intense neuronal degeneration in the GCL and in the inner nuclear layer than in sham-operated retinas. A single intraocular injection of capsazepine (100 mu M), a TRPV1 antagonist, 5 days after optic nerve lesion, decreased the number of GFAP-expressing Muller cells (72.5% of control values) and also decreased protein nitration in the retinal vitreal margin (75.7% of control values), but did not affect lipid peroxidation. Furthermore, retinal explants were treated with capsaicin (100 mu M), and remarkable protein nitration was then present, which was reduced by blockers of the constitutive and inducible nitric oxide synthases (7-NI and aminoguanidine, respectively). TRPV1 activation also increased GFAP expression, which was reverted by both TRPV1 antagonism with capsazepine and by 7-NI and aminoguanidine. Given that Muller cells do not express TRPV1, we suppose that the increased GFAP expression in these cells might be elicited by TRPV1 activation and by its indirect effect upon nitric oxide overproduction and peroxynitrite formation. We incubated Fluorogold pre-labeled retinal explants in the presence of capsazepine (1 mu M) during 48 h. The numbers of surviving RGCs stained with fluorogold and the numbers of apoptotic cells in the GCL detected with TUNEL were similar in lesioned and control retinas. We conclude that TRPV1 receptor expression decreased after optic nerve injury due to death of TRPV1-containing cells. Furthermore, these data indicate that TRPV1 might be involved in intrinsic protein nitration and Muller cell reaction observed after optic nerve injury. (C) 2010 Elsevier Ltd. All rights reserved.

Connexin-mediated communication controls cell proliferation and is essential in retinal histogenesis

Connexin (Cx) channels and hemichannels are involved in essential processes during nervous system development such as apoptosis, propagation of spontaneous activity and interkinetic nuclear movement. In the first part of this study, we extensively characterized Cx gene and protein expression during retinal histogenesis. We observed distinct spatio-temporal patterns among Studied Cx and an overriding, ubiquitous presence of Cx45 in progenitor cells. The role of Cx-mediated communication was assessed by using broad-spectrum (carbenoxotone, CBX) and Cx36/Cx50 channel-specific (quinine) blockers. In vivo application of CBX, but not quinine, caused remarkable reduction in retinal thickness, suggesting changes in cell proliferation/apoptosis ratio. Indeed, we observed a decreased number of mitotic cells in CBX-injected retinas, with no significant changes in the expression of PCNA, a marker for cells in proliferative state. Taken together, Our results pointed a pivotal role of Cx45 in the developing retina. Moreover, this study revealed that Cx-mediated Communication is essential in retinal histogenesis, particularly in the control of cell proliferation. (C) 2009 ISDN. Published by Elsevier Ltd. All rights reserved.

Effects of mercury intoxication on the response of horizontal cells of the retina of thraira fish (Hoplias malabaricus)

Methyl mercury (MeHg) is highly neurotoxic, affecting visual function in addition to other central nervous system functions. The effect of mercury intoxication on the amplitude of horizontal cell responses to light was studied in the retina of the fish Hoplias malabaricus. Intracellular responses were recorded from horizontal cells of fish previously intoxicated with MeHg by intraperitoneal injection (IP group) or by trophic exposure (T group). Only one retina per fish was used. The doses of MeHg chloride administered to the IP group were 0.01, 0.05, 0.1, 1.0, 2.0, and 6.0 mg/kg. The amplitudes of the horizontal cell responses were lower than control in individuals exposed to 0.01 (N = 4 retinas), 0.05 (N = 2 retinas) and 0.1 mg/kg (N = 1 retina), whereas no responses were recorded in the 1.0, 2.0, and 6.0 mg/kg groups. T group individuals were fed young specimens of Astyanax sp previously injected with MeHg corresponding to 0.75 (N = 1 retina), 0.075 (N = 8 retinas) or 0.0075 (N = 4 retinas) mg/kg fish body weight. After 14 doses, one every 5 days, the amplitude of the horizontal cell response was higher than control in individuals exposed to 0.075 and 0.0075 mg/kg, and lower in individuals exposed to 0.75 mg/kg. We conclude that intoxication with MeHg affects the electrophysiological response of the horizontal cells in the retina, either reducing or increasing its amplitude compared to control, and that these effects are related to the dose and/or to the mode of administration.

Efeito do tratamento com as drogas antipsicóticas haloperidol e clozapina sobre a infecção de toxoplasma gondii em cultura de células retinianas embrionárias

T. gondii is an obligate intracellular protozoan and the main cause of retinochoroiditis in humans. The aim of this study was to evaluate the effect of the antipsychotic drugs haloperidol and clozapine on the course of infection by T. gondii of cultured embryonic retinal cells. Embryo retinas of Gallus gallus domesticus (E12) were used for the preparation of mixed monolayer cultures of retinal cells. Cultures were maintained on plates of 96 and 24 wells by 37°C in DMEM medium supplemented with 5% fetal bovine serum for 2 days. After this period, cultures were simultaneously infected with tachyzoites of T. gondii and treated with the antipsychotics haloperidol and clozapine for 48 hours. Treatment effects were determined by both assessing cell viability with the MTT method and evaluating infection outcomes in slides stained with Giemsa. The treatment with haloperidol and clozapine cells infected with T. gondii resulted in higher viability of these cells, suggesting a possible prevention of neuronal degeneration induced by T. gondii. Additionally, intracellular replication of this protozoan in cells treated with haloperidol and clozapine were significantly reduced, possibly by modulation of the parasite s intracellular calcium concentration

Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration

Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. Thus, we analysed the morphology and apoptosis index in retinas of obese rats in whom insulin resistance had been induced by a high-fat diet (HFD). Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT1, eNOS and nNOS protein than those of samples taken from control animals. Furthermore, immunohistochemical analyses indicated higher levels of iNOS and 4-hydroxynonenal and a larger number of apoptotic nuclei in HFD rats. Finally, both the inner and outer retinal layers of HFD rats were thinner than those in their control counterparts. When considered alongside previous results, these patterns suggest two major ways in which HFD might impact animals: direct activity of ingested fatty acids and/or via insulin-resistance-induced changes in intracellular pathways. We discuss these possibilities in further detail and advocate the use of this animal model for further understanding relationships between retinopathy, metabolic syndrome and type 2 diabetes. © 2012 John Wiley & Sons, Ltd.

Methylmercury intoxication activates nitric oxide synthase in chick retinal cell culture

The visual system is a potential target for methylmercury (MeHg) intoxication. Nevertheless, there are few studies about the cellular mechanisms of toxicity induced by MeHg in retinal cells. Various reports have indicated a critical role for nitric oxide synthase (NOS) activation in modulating MeHg neurotoxicity in cerebellar and cortical regions. The aim of the present study is to describe the effects of MeHg on cell viability and NOS activation in chick retinal cell cultures. For this purpose, primary cultures were prepared from 7-day-old chick embryos: retinas were aseptically dissected and dissociated and cells were grown at 37ºC for 7-8 days. Cultures were exposed to MeHg (10 µM, 100 µM, and 1 mM) for 2, 4, and 6 h. Cell viability was measured by MTT method and NOS activity by monitoring the conversion of L-[H3]-arginine to L-[H3]-citrulline. The incubation of cultured retina cells with 10 and 100 µM MeHg promoted an increase of NOS activity compared to control (P < 0.05). Maximum values (P < 0.05) were reached after 4 h of MeHg incubation: increases of 81.6 ± 5.3 and 91.3 ± 3.7%, respectively (data are reported as mean ± SEM for 4 replicates). MeHg also promoted a concentration- and time-dependent decrease in cell viability, with the highest toxicity (a reduction of about 80% in cell viability) being observed at the concentration of 1 mM and after 4-6 h of incubation. The present study demonstrates for the first time the modulation of MeHg neurotoxicity in retinal cells by the nitrergic system

Density, proportion, and dendritic coverage of retinal ganglion cells of the common marmoset (Callithrix jacchus jacchus)

We performed a quantitative analysis of M and P cell mosaics of the common-marmoset retina. Ganglion cells were labeled retrogradely from optic nerve deposits of Biocytin. The labeling was visualized using horseradish peroxidase (HRP) histochemistry and 3-3'diaminobenzidine as chromogen. M and P cells were morphologically similar to those found in Old- and New-World primates. Measurements were performed on well-stained cells from 4 retinas of different animals. We analyzed separate mosaics for inner and outer M and P cells at increasing distances from the fovea (2.5-9 mm of eccentricity) to estimate cell density, proportion, and dendritic coverage. M cell density decreased towards the retinal periphery in all quadrants. M cell density was higher in the nasal quadrant than in other retinal regions at similar eccentricities, reaching about 740 cells/mm2 at 2.5 mm of temporal eccentricity, and representing 8-14% of all ganglion cells. P cell density increased from peripheral to more central regions, reaching about 5540 cells/mm2 at 2.5 mm of temporal eccentricity. P cells represented a smaller proportion of all ganglion cells in the nasal quadrant than in other quadrants, and their numbers increased towards central retinal regions. The M cell coverage factor ranged from 5 to 12 and the P cell coverage factor ranged from 1 to 3 in the nasal quadrant and from 5 to 12 in the other quadrants. These results show that central and peripheral retinal regions differ in terms of cell class proportions and dendritic coverage, and their properties do not result from simply scaling down cell density. Therefore, differences in functional properties between central and peripheral vision should take these distinct regional retinal characteristics into account.

Efeito protetor da flavana extraída da espécie Brosimum acutifolium contra danos causados por hipóxia em células retinianas: um estudo in vitro

O acidente vascular cerebral isquêmico (AVCi) causa danos celulares por provocar intensa excitotoxicidade e estresse oxidativo após privação de oxigênio e glicose para uma região do encéfalo. Neste trabalho, investigamos o potencial neuroprotetor da planta amazônica Brosimum acutifolium que é rica em flavanas como a 4',7-diidroxi-8-(3,3-dimetilalil)flavana (brosimina b, aqui abreviada como Bb) que apresenta elevado potencial antioxidante. Utilizamos cultura de células retinianas de embrião de galinha submetidas a hipóxia experimental, por privação de oxigênio e glicose, para avaliarmos o potencial antioxidante da Bb através da análise do sequestro do radical 2,2-difenil-1-picril-hidrazil (DPPH). Além disso, avaliamos a viabilidade celular (VC) e o perfil oxidativo e antioxidativo após 3, 6 e 24 horas de hipóxia, pela produção de oxigênio reativo (O₂^-) e atividade antioxidante endógena pela enzima catalase, respectivamente. Nossos resultados demonstram que nosso modelo experimental de hipóxia in vitro provoca redução tempo-dependente da VC, acompanhada por intenso estrese oxidativo, devido à excessiva produção de oxigênio reativo (O₂^-). O tratamento com Bb (10μM) protegeu significativamente a viabilidade celular durante 3 e 6 h de hipóxia experimental em células retiniana cultivadas in vitro, além de favorecer o aumento da atividade da enzima catalase em todos os tempos testados. Desta forma, concluímos que a Bb possui ação antioxidante e neuroprotetor por contribuir na defesa contra o estresse oxidativo induzido em condições de hipóxia, tornando-se como uma droga com potencial uso em tratamentos em casos de AVCi in vivo.

Análise morfológica e topográfica das células ganglionares da retina do caititu (Tayassu tajacu)

Na Amazônia habitam diversas espécies de animais silvestres, tornando-a um importante local de investigação sobre fisiologia comparada. Dentre estas espécies, destacamos o caititu Tayassu tajacu, animal distribuído na América Central e Latina. Existem várias publicações acerca da morfologia de órgãos sexuais, carne e sangue do caititu. Porém, no que diz respeito ao estudo sobre a morfofisiologia visual do caititu, as publicações ainda são escassas. Diante dessa realidade, o presente estudo investigou a morfologia e topografia das células ganglionares da retina do Tayassu tajacu. Foram utilizadas seis retinas, provenientes de oito animais de ambos os sexos da espécie Tayassu tacaju. Os caititus, criados e mantidos em cativeiro na Empresa Brasileira de Pesquisa Brasileira - Embrapa/Pará, foram abatidos de acordo com as normas de manejo animal para posterior retirada e fixação dos olhos. As retinas foram dissecadas e coradas utilizando a técnica de Nissl para visualização de células ganglionares, amácrinas deslocadas, hemácias, micróglia e células componentes da vascularização. A contagem de células ganglionares foi realizada ao longo do eixo horizontal e vertical, sendo o número de células ganglionares por campo convertido em valores de densidade. Diferentes regiões da retina foram analisadas quanto à densidade celular, obtendo-se como valor médio de densidade 351,822 ± 31,434 CG/mm². Verificaram-se diferenças de densidade entre as regiões estudadas: a região dorsal teve densidade média e desvio padrão de 894 ± 44 CG/mm²; a região ventral 894 ± 1 CG/mm²; a região nasal 1.403 ± 43; e a região temporal com 1596 ± 251. O pico de densidade a média, localizado a aproximadamente 3,13 mm de distância no sentido dorsal e 6,77 mm no sentido temporal do nervo óptico, foi de 6.767 CG/mm². Verificaram-se duas regiões especializadas, a faixa visual e a area temporalis. A faixa visual, localizada no sentido horizontal da região nasal para temporal, apresentou alta densidade celular, possivelmente proporcionando melhor visão panorâmica do ambiente e detecção de objetos em movimento no horizonte. Já a area temporalis, localizada dentro da faixa visual, proporciona maior acuidade visual e resolução espacial, do meio em que vivem Os resultados deste trabalho permitem iniciar comparações morfofisiológicas da retina dos caititus com a de outras espécies animais.

Losses of immunoreactive parvalbumin amacrine and immunoreactive alphaprotein kinase C bipolar cells caused by methylmercury chloride intoxication in the retina of the tropical fish Hoplias malabaricus

To quantify the effects of methylmercury (MeHg) on amacrine and on ON-bipolar cells in the retina, experiments were performed in MeHg-exposed groups of adult trahiras (Hoplias malabaricus) at two dose levels (2 and 6 µg/g, ip). The retinas of test and control groups were processed by mouse anti-parvalbumin and rabbit anti-_aprotein kinase C (_aPKC) immunocytochemistry. Morphology and soma location in the inner nuclear layer were used to identify immunoreactive parvalbumin (PV-IR) and _aPKC (_aPKC-IR) in wholemount preparations. Cell density, topography and isodensity maps were estimated using confocal images. PV-IR was detected in amacrine cells in the inner nuclear layer and in displaced amacrine cells from the ganglion cell layer, and _aPKC-IR was detected in ON-bipolar cells. The MeHg-treated group (6 µg/g) showed significant reduction of the ON-bipolar _aPKC-IR cell density (mean density = 1306 ± 393 cells/mm²) compared to control (1886 ± 892 cells/mm²; P < 0.001). The mean densities found for amacrine PV-IR cells in MeHg-treated retinas were 1040 ± 56 cells/mm² (2 µg/g) and 845 ± 82 cells/mm² (6 µg/g), also lower than control (1312 ± 31 cells/mm²; P < 0.05), differently from the data observed in displaced PV-IR amacrine cells. These results show that MeHg changed the PV-IR amacrine cell density in a dose-dependent way, and reduced the density of _aKC-IR bipolar cells at the dose of 6 µg/g. Further studies are needed to identify the physiological impact of these findings on visual function.

O fator de crescimento do nervo inibe o edema citotóxico de células de Müller e células bipolares da retina de rato por meio da liberação de citocinas gliais: participação do sistema glutamatérgico e purinérgico

O fator de crescimento do nervo (NGF) pode retardar a degeneração celular na retina de ratos em diferentes injúrias retinianas. O acúmulo de água em células da retina contribui para o desenvolvimento de edema retiniano e degeneração neuronal. Em atribuição ao seu efeito protetor, este trabalho teve por objetivo avaliar se o NGF influencia o edema celular osmótico em células de Müller e células bipolares. Assim, montagens planas, fatias de retina e células isoladas da retina de ratos foram superfundidas com solução hipo-osmótica na presença de BaCl₂. Secções retinianas foram utilizadas para imunomarcações, e a liberação de adenosina foi medida por cromatografia líquida de alta eficácia, em montagens planas. A área de secção transversal celular foi medida antes e após a superfusão em meio hipo-osmótico, em fatias de retina e suspensões celulares. Tanto células de Müller quanto células bipolares foram imunopositivas para TrkA, mas somente células de Müller foram marcadas contra p75^NTR e NGF. A hipo-osmolaridade induziu um rápido e significativo aumento da liberação de adenosina endógena em retinas controle, mas não em retinas perfundidas com BaCl₂. O NGF inibiu o edema citotóxico em células de Müller e em células bipolares em fatias de retina controle e retinas pós-isquêmicas submetidas a condições hipo-osmóticas. Por outro lado, NGF impediu o edema citotóxico da célula de Müller isolada, mas não da célula bipolar isolada (em meio hipo-osmótico contendo íons Ba²⁺). Isto sugere que NGF induz a liberação de fatores por células de Müller, os quais inibem o edema citotóxico de células bipolares em fatias de retina. O efeito inibitório do NGF sobre o edema citotóxico de células de Müller foi mediado pela ativação do receptor TrkA, mas não de p75^NTR, e foi anulado por bloqueadores de receptores metabotrópicos de glutamato, receptores de adenosina A₁, e receptores do fator de crescimento de fibroblasto (FGF). O bFGF evitou o edema citotóxico de células de Müller isoladas, mas inibiu somente em parte o edema citotóxico de células bipolares isoladas. O bloqueio de FGFR impediu o efeito inibidor de edema celular da adenosina, sugerindo que a liberação de bFGF ocorre após à ativação autócrina/parácrina de receptores A_l. Além de bFGF, GDNF e TGF431 reduziram em parte o edema citotóxico da célula bipolar. Estes dados sugerem que o efeito neuroprotetor do NGF é em parte mediado pela prevenção de edema citotóxico de células gliais e bipolares da retina.