Phosphorylation of Glycogen Synthase Kinase-3beta(S9) Induced Neuronal Cell Survival by Sulindac in the Rat Retina

ABSTRACT

PURPOSE: Inactivation of glycogen synthase kinase-3beta (GSK-3beta) by S9 phosphorylation is implicated in neuronal cell survival. In this study, we examined the involvement of GSK-3betaS9) phosphorylation on retina cell survival by sulindac (SLD) in model of retina ischemia. METHODS: Retinal ischemia was induced by increasing intraocular pressure to a range of 160 mm Hg to 180 mm Hg for 60 minutes in adult rats. SLD was treated pre and after (0.01 to 0.1 mM) ischemic injury. In vitro study, the retinas were isolated at postnatal 1-2day and were used to glutamate for ischemic injury. For morphological study, retinas were embedded in resin 24 hours after ischemic injury. The patterns of retinal cell were determined using light microscopy. Western blot analysis was performed using GSK-3beta(S9) and phospho-GSK-3beta(S9) antibodies. RESULTS: In ischemic animal model, cell death with necrosis and apoptosis was observed, treatment with SLD was reduced cell death. In vitro study, treatment of glutamate were reduce dose dependent manners, SLD treatment were decrease retina cell death. Western blot analysis of GSK-3beta(S9) phosphorylation known to induce neuronal cell survival, were increased in the SLD treated retina in ischemic injury. CONCLUSIONS: This study suggest that GSK-3beta(S9) is one of the effect by which SLD treatment protect retina from neuronal cell death.