The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice
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1Affiliated Eye Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China;
2Jiangxi Research Institute of Ophthalmology and Visual Sciences, Nanchang 330006, Jiangxi Province, China;
3Department of Ophthalmology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China

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Supported byNational Natural Science Foundation of China (No.81160118, 81400372); Clinical Medicine Research Special-purpose Foundation of China (No.L2012052); Jiangxi Province Sailing Engineering (No.2014022); Science Technology Foundation of Jiangxi Province (No.20151BBG70223); Youth Science Foundation of Jiangxi Province (No.20151BAB215016); Education Department Youth Scientific Research Foundation (No.GJJ14170); Health Development Planning Commission Science Foundation of Jiangxi Province (NO:20155154); Health Department Tradition Chinese Medicine Science and Technology Foundation (No.2010A015, 2012A139, 2013A073).

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    Abstract:

    AIM:To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE+/- mice (AChE 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/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE+/- mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient 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 AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer.RESULTS:Different concentrations of H2O2 induced AChE 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 AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.

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Yun-Min Yi, Li Cai, Yi Shao, et al. The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice. Int J Ophthalmol, 2015,8(5):884-890

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Publication History
  • Received:June 24,2014
  • Revised:March 09,2015
  • Adopted:March 09,2015
  • Online: October 09,2015
  • Published: