Inhibition of GSK-3β activity decreases photoreceptor cell death in rat retina

Photoreceptor cell death leading to retinal degeneration could be induced by physical or chemical treatments. However, the progress of photoreceptor cell death and underlying cellular and molecular mechanisms remain largely unexplored. Our previous studies have shown that Phosphatidylinositol-3-kinase (PI3K) signaling could mediate the effect of 17β-Estradiol (βE2) which protects photoreceptor cells from death. In present study, we report a novel finding that phosphorylation of glycogen synthase kinase-3β (GSK-3β) controlled by PI3K/Akt signaling is a potent mediator in photoreceptor cell death. In two different animal models of retinal degeneration, light-damaged or N-Methyl-N-nitrosourea (MNU)-induced, GSK-3β phosphorylation was inhibited. Furthermore, phosphorylating Ser9 of GSK-3β with Lithium chloride (LiCl) was able to protect photoreceptor cells, whereas inhibition of the PI3K/Akt with LY294002 which decreases GSK-3β phosphorylation could not protect retinal cells from death. Our results suggest GSK-3β activity is closely related to photoreceptor cell death, and the application of GSK-3β inhibitor LiCl can reduce photoreceptor cell death in retinal degeneration.