TrkB-T1 Receptors on Muller Cells Play Critical Role in Brain-Derived Neurotrophic Factor-Mediated Photoreceptor Protection against Phototoxicity

Abstract

PURPOSE: To determine how brain-derived neurotrophic factor (BDNF) protects photoreceptors against phototoxicity. METHODS: Iris pigment epithelial cells (IPE) that were transduced with different concentrations of adeno-associated virus (AAV) mediated BDNF (AAV-BDNF-IPE) were transplanted into the subretinal space of rats. We also injected small interfering RNAs (siRNAs) for TrkB, a BDNF receptor. The rats were exposed to continuous light to induce phototoxicity. We examined the expression of TrkB in the retina by Western blot and immunohistochemistry. RESULTS: Significant photoreceptor protection was detected when more than 1 x 10(7) capsids/ml AAV-BDNF was transplanted. An intravitreal injection of siRNAs showed that the photoreceptor protection by AAV-BDNF-IPE was reduced by injecting the siRNA of TrkB-T1, one of the TrkB isoforms. TrkB-T1 was slightly upregulated by Western blot, and one of the cells that upregulated TrkB-T1 was Muller cells by immunohistochemistry. CONCLUSION: We conclude that Muller cells are one of the cells responsible for the expression of TrkBs, and TrkB-T1 may play a role in the protection of photoreceptors against phototoxicity.