Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration

Prolonged or high-intensity exposure to visible light leads to photoreceptor cell death. In this study, we demonstrate a novel pathway of light-induced photoreceptor apoptosis involving the low-affinity neurotrophin receptor p75 (p75(NTR)). Retinal degeneration upregulated both p75(NTR) and the high-affinity neurotrophin receptor TrkC in different parts of Muller glial cells. Exogenous neurotrophin-3 (NT-3) increased, but nerve growth factor (NGF) decreased basic fibroblast growth factor (bFGF) production in Muller cells, which can directly rescue photoreceptor apoptosis. Blockade of p75(NTR) prevented bFGF reduction and resulted in both structural and functional photoreceptor survival in vivo. Furthermore, the absence of p75(NTR) significantly prevented light-induced photoreceptor apoptosis. These observations implicate glial cells in the determination of neural cell survival, and suggest functional glial-neuronal cell interactions as new therapeutic targets for neurodegeneration.