Inhibition of GSK-3β Activation Protects SD Rat Retina Against N-Methyl-N-Nitrosourea-Induced Degeneration by Modulating the Wnt/β-Catenin Signaling Pathway

Retinal degenerative diseases are characterized by photoreceptor cell loss. Photoreceptor cell loss leading to retinal degeneration can be induced by N-methyl-N-nitrosourea (MNU), which was widely used to mimic the pathology. However, the mechanism by which MNU induces photoreceptor cell loss is still largely unknown. The purpose of the present study was to investigate whether phosphorylation of glycogen synthase kinase-3 beta (p-GSK-3 beta) is a potent mediator of MNU-induced retinal degeneration and how p-GSK-3 beta affects the process. MNU-induced photoreceptor cell loss was evaluated in Sprague-Dawley (SD) rat retinas. GSK-3 beta and Akt expression levels did not change during MNU-induced retinal degeneration but the phosphorylation of GSK-3 beta and Akt was decreased by MNU treatment. Lithium chloride (LiCl), which increases p-GSK-3 beta level and active-beta-catenin level, reversed retinal degeneration induced by MNU treatment. These results suggest that GSK-3 beta activation is closely related to photoreceptor cell loss and that the application of the GSK-3 beta inhibitor LiCl could activate Wnt/beta-catenin signaling pathway and reduce photoreceptor cell loss induced by MNU. Our findings indicate that inhibition of GSK-3 beta activation may be a potential therapeutic target for retinal degeneration induced by photoreceptor cell loss.