AChE Deficiency Or Inhibition Decreases Apoptosis And Caspase3Expression In RPE And Photoreceptors Induced By Sodium Iodate

Objective:To investigated AchE expression in photoreceptor apoptosis induced by retinal toxicity,and whether AChE deficiency or inhibition can protect against apoptosis caused by NaI03.Methods:C57BL mice from each time points were injected via the orbital venous plexus with NaIO3(50mg/kg),and euthanatized6h,ld,3d,or7days after NaI03administration. Donepezil-treated group were administered different dose (0.5、2.5、12.5mg/kg) for3days by gavage, then were injected with NaIO3(50mg/kg) on the third day. Naringin-treated group were administered different dose(30>60mg/kg) for1day by gavage, then were injected with NaIO3(50mg/kg) on the second day.Mice pretreated with AChE inhibitors were euthanatized3days after NaIO3administration.Heterozygous AChE-deficient mice and Wild type mice were injected with NaIO3(25mg/kg),and euthanatized3days later.Eyes were enucleated and collect the retina. The apotosis of photoreceptor were analysed by TUNEL staining. Immunefluorescence and western blot were respectively detected the expression of Caspase-3and AchE.Results:In this study,Administration of NaIO3(50mg/kg) caused significant photoreceptor apoptosis and the peak was found on the3rd day. Immunefluorescence and western blot showed that AchE and Caspase-3expression during apoptosis induced by NaIO3.In addition,both genetic AChE deficiency and chemical inhibition of AChE significantly reduced the apoptosis. Activation of caspases-3in vivo were prevented and associated with reduced levels of cell death.Conclusions:Our study demonstrates that AChE may be a pro-apoptotic factor and the inhibition of AChE reduces photoreceptor apoptosis. Both genetic AChE deficiency and chemical inhibition of AChE significantly reduced the apoptosis by block the activation of caspases-3.These findings suggest that AChE inhibitors may represent a therapeutic strategy for protection against retinal degeneration.