Alternate FGF2-ERK1/2 signaling pathways in retinal photoreceptor and glial cells in vitro

Basic fibroblast growth factor (FGF2) stimulates photoreceptor survival in vivo and in vitro, but the molecular signaling mechanism(s) involved are un known. Immunohistochemical and immunoblotting analyses of pure photorecepto rs, inner retinal neurons, and Muller glial cells (MGC) in vitro revealed d ifferential expression of the high affinity FGF receptors (FGFR1-4), as wel l as many cytoplasmic signaling intermediates known to mediate the extracel lular signal-regulated kinase (ERK1/2) pathway. FGF2-induced tyrosine phosp horylation in vitro exhibited distinct profiles for each culture type, and FGF2-induced ERK1/2 activation was observed for all three preparations. Whe reas U0126, a specific inhibitor of ERK kinase (MEK), completely abolished FGF2-induced ERK1/2 tyrosine phosphorylation and survival in cultured photo receptors, persistent ERK1/2 phosphorylation was observed in cultured inner retinal cells and MGC. Furthermore U0126 treatment entirely blocked nerve growth factor-induced ERK1/2 activation in MGC, as well as FGF2-induced ERK 1/2 activation in cerebral glial cells. Taken together, these data indicate that FGF2-induced ERK1/2 activation is entirely mediated by MEK within pho toreceptors, which is responsible for FGF2-stimulated photoreceptor surviva l. In contrast, inner retina/glia possess alternative, cell type, and growt h factor-specific MEK-independent ERK1/2 activation pathways. Hence signali ng and biological effects elicited by FGF2 within retina are mediated by ce ll type-specific pathways.