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Neuroscience ; 295: 175-86, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-25813711

RESUMO

Water accumulation in retinal glial (Müller) and neuronal cells resulting in cellular swelling contributes to the development of retinal edema and neurodegeneration. Intravitreal administration of neurotrophins such as brain-derived neurotrophic factor (BDNF) is known to promote survival of retinal neurons. Here, we show that exogenous BDNF inhibits the osmotic swelling of Müller cell somata induced by superfusion of rat retinal slices or freshly isolated cells with a hypoosmotic solution containing barium ions. BDNF also inhibited the osmotic swelling of bipolar cell somata in retinal slices, but failed to inhibit the osmotic soma swelling of freshly isolated bipolar cells. The inhibitory effect of BDNF on Müller cell swelling was mediated by activation of tropomyosin-related kinase B (TrkB) and transactivation of fibroblast growth factor receptors. Exogenous basic fibroblast growth factor (bFGF) fully inhibited the osmotic swelling of Müller cell somata while it partially inhibited the osmotic swelling of bipolar cell somata. Isolated Müller cells displayed immunoreactivity of truncated TrkB, but not full-length TrkB. Isolated rod bipolar cells displayed immunoreactivities of both TrkB isoforms. Data suggest that the neuroprotective effect of exogenous BDNF in the retina is in part mediated by prevention of the cytotoxic swelling of retinal glial and bipolar cells. While BDNF directly acts on Müller cells by activation of TrkB, BDNF indirectly acts on bipolar cells by inducing glial release of factors like bFGF that inhibit bipolar cell swelling.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/farmacologia , Edema/tratamento farmacológico , Células Ependimogliais/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/metabolismo , Células Bipolares da Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Análise de Variância , Animais , Bário/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Edema/etiologia , Feminino , Técnicas In Vitro , Masculino , Pressão Osmótica , Proteína Quinase C/metabolismo , Ratos , Ratos Long-Evans , Receptor trkB/metabolismo , Retina/citologia , Estatísticas não Paramétricas , Fatores de Tempo
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