The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice

• 作者: Jing-Lin Yi Li Cai Man Xu Yi Shao Yun-Min Yi
• 来源期刊: 国际眼科杂志：英文版
• 学科: 医学
• 关键词: 网膜的颜料上皮 ACETYLCHOLINESTERASE apoptosis 疼痛 ^+/− 动物模型 acetylcholinesterase 禁止者
• 年，卷（期）: 2015,（5）
• 页码范围: 884-890
• 页数: 0页
• 分类号: R774.1

摘要

AIM: To determine the effect of different concentrations of the acetylcholinesterase(ACh E)inhibitors tacrine and donepezil on retinal protection in AChE+/- mice(ACh E knockout mice) of various ages.·METHODS: Cultured ARPE-19 cells were treated with hydrogen peroxide(H2O2) at concentrations of 0, 250,500, 1000 and 2000 μmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil( 0. 1 mg / m L, 0. 2 mg / m L and0.4 mg/m L) were respectively given to AChE+/- mice aged2 mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline(PBS) was administered to the control group. The mice were sacrificed after 30 d by in vitro cardiac perfusion and retinal samples were taken. ACh Edeficient mice were identified by polymerase chain reaction(PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website.H&E staining, immunofluorescence and Western blot were performed to observe ACh E protein expression changes in the retinal pigment epithelial(RPE) cell layer.·RESULTS: Different concentrations of H2O2 induced ACh E expression during RPE cell apoptosis. AChE+/- mice retina were thinner than those in wild-type mice(P <0.05); the retinal structure was still intact at 2mo but became thinner with increasing age(P <0.05); furthermore,AChE+/- mice developed more slowly than wild-type mice(P <0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology(P >0.05).·CONCLUSION: In vivo, tacrine and donepezil can inhibit the expression of ACh E; the decrease of ACh E expression in the retina is beneficial for the development of the retina.