Int J Ophthalmol. 2015 Oct 18;8(5):884-90. doi: 10.3980/j.issn.2222-3959.2015.05.06. eCollection 2015.
The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice.
International journal of ophthalmology
Yun-Min Yi, Li Cai, Yi Shao, Man Xu, Jing-Lin Yi
Affiliations
Affiliations
- Affiliated Eye Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
- Jiangxi Research Institute of Ophthalmology and Visual Sciences, Nanchang 330006, Jiangxi Province, China.
- Department of Ophthalmology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
PMID: 26558196
PMCID: PMC4631000 DOI: 10.3980/j.issn.2222-3959.2015.05.06
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.
Keywords: AChE+/− animal models; acetylcholinesterase; acetylcholinesterase inhibitors; apoptosis; retinal pigment epithelium
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