lithium-chloride and Retinal-Degeneration

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-3β (p-GSK-3β) is a potent mediator of MNU-induced retinal degeneration and how p-GSK-3β affects the process. MNU-induced photoreceptor cell loss was evaluated in Sprague-Dawley (SD) rat retinas. GSK-3β and Akt expression levels did not change during MNU-induced retinal degeneration but the phosphorylation of GSK-3β and Akt was decreased by MNU treatment. Lithium chloride (LiCl), which increases p-GSK-3β level and active-β-catenin level, reversed retinal degeneration induced by MNU treatment. These results suggest that GSK-3β activation is closely related to photoreceptor cell loss and that the application of the GSK-3β inhibitor LiCl could activate Wnt/β-catenin signaling pathway and reduce photoreceptor cell loss induced by MNU. Our findings indicate that inhibition of GSK-3β activation may be a potential therapeutic target for retinal degeneration induced by photoreceptor cell loss.

Topics: Animals; beta Catenin; Enzyme Inhibitors; Glycogen Synthase Kinase 3 beta; Lithium Chloride; Male; Methylnitrosourea; Rats; Rats, Sprague-Dawley; Retina; Retinal Degeneration; Wnt Signaling Pathway

To investigate the effect of carbachol on the phagocytosis of photoreceptor outer segments (OS) in cultures of normal Long-Evans and dystrophic Royal College of Surgeons (RCS) rat retinal pigment epithelial (RPE) cells.. Retinal pigment epithelial cells from normal and RCS rats were grown in tissue culture. On reaching confluence, they were presented with OS suspended in Krebs-Henseleit buffer in the presence or absence of carbachol and LiCl. The number of bound and ingested OS was quantitated using double immunofluorescence staining.. LiCl inhibited the ingestion of OS by more than 90% but had no effect on the binding of OS by Long-Evans RPE cells. The addition of carbachol further reduced OS ingestion. Carbachol alone decreased OS ingestion by normal RPE cells by 30% but had no effect on OS binding. The effect of LiCl and carbachol on RCS RPE cells was similar to their effect on normal RPE cells.. Carbachol does not increase OS phagocytosis in normal or RCS rat RPE cells. The phagocytic defect in RCS rat RPE cannot be reversed or overcome by stimulation of the IP3 pathway by carbachol. LiCl strongly inhibits the ingestion of OS by normal and by RCS RPE cells, and this effect is enhanced by carbachol.

Topics: Animals; Carbachol; Cells, Cultured; Inositol 1,4,5-Trisphosphate; Lithium Chloride; Phagocytosis; Pigment Epithelium of Eye; Rats; Rats, Mutant Strains; Retinal Degeneration; Rod Cell Outer Segment