RESUMO
PURPOSE: To investigate whether electrical stimulation promoted axonal regeneration of retinal ganglion cells (RGCs) after optic nerve (ON) crush in adult rats. METHODS: Transcorneal electrical stimulation (TES), which stimulates the retina with current from a corneal contact lens electrode, was used to stimulate the eye. TES was applied for 1 h immediately after ON crush. Axonal regeneration was determined by anterograde labeling of RGC axons. To examine whether the axonal regeneration was mediated by insulin-like growth factor 1 (IGF-1) receptors, an IGF-1 receptor antagonist, JB3, was injected intraperitoneally before each TES application. Immunostaining for IGF-1 was performed to examine the effects of TES. To test the survival-promoting effects of TES applied daily, the mean density of retrogradely labeled RGCs was determined on day 12 after ON crush. RESULTS: Compared with sham stimulation, the mean number of regenerating axons significantly increased at 250 microm distal from the lesion and increased IGF-1 immunoreactivity was observed in retinas treated daily with TES. Preinjection of an IGF-1 receptor antagonist significantly blocked axonal regeneration by TES applied daily. TES applied daily also markedly enhanced the survival of RGCs 12 days after ON crush. CONCLUSION: TES applied daily promotes both axonal regeneration and survival of RGCs after ON crush.
Assuntos
Axônios/fisiologia , Terapia por Estimulação Elétrica , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Óptico/fisiopatologia , Células Ganglionares da Retina/fisiologia , Animais , Contagem de Células , Sobrevivência Celular , Técnica Indireta de Fluorescência para Anticorpo , Fator de Crescimento Insulin-Like I/análogos & derivados , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Masculino , Compressão Nervosa , Traumatismos do Nervo Óptico/metabolismo , Ratos , Ratos Wistar , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/metabolismo , Regulação para CimaRESUMO
Xylazine, an alpha-2 adrenergic agonist, activates the endogenous trophic factors and neuronal survival signaling. Here, we tested the regenerative effect of xylazine on damaged optic nerve axons in adult rats. After optic nerve crush, xylazine was intraperitoneally injected into three groups of rats: a single administration immediately after the crush, intermittent administration, and daily administration. On day 14, the regenerated axons were quantitatively evaluated by anterograde labeling. Everyday administration but neither single nor intermittent administration markedly increased the number of labeled axons beyond the crush site, with upregulation of growth-associated protein-43 in the ganglion cell layer and the regenerated axons. It was concluded that xylazine promotes axonal regeneration in damaged optic nerves of adult rats.