Acetylcholinesterase inhibition ameliorates retinal neovascularization and glial activation in oxygen-induced retinopathy

作     者：Qiu-Ping Liu Xian Zhang Ya-Zhou Qin Jing-Lin Yi Jing-Ming Li 

作者机构：Affiliated Eye Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of OphthalmologyFirst Affiliated Hospital of Xi'an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina 

出 版 物：《International Journal of Ophthalmology(English edition)》 (国际眼科杂志（英文版）)

年 卷 期：2020年第13卷第9期

页      面：1361-1367页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

基　　金：Supported by National Natural Science Foundation of China(No.81960177,No.81741058,No.81400427,No.81460163,No.81300786) Grants from Jiangxi Science and Technology Department(No.20192BAB205049,No.20142BDH80005,No.20142BAB215029,No.20132BAB205024) Research Grants from Jiangxi Education Department(No.GJJ14094,No.GJJ13175)。 

主　　题：acetylcholinesterase oxygen-induced retinopathy neovascularization glosis mice 

摘      要：AIM:To investigate whether inhibition of acetylcholinesterase(AChE)by donepezil ameliorate aberrant retinal neovascularization(RNV)and abnormal glial activation in oxygen-induced retinopathy(OIR).METHODS:A mouse model of RNV was induced in postnatal day 7(P7)mice by exposure to 75%oxygen.Donepezil was administrated to P12 mice by intraperitoneal injection.Expression and localization of AChE in mouse retinas were determined by immunofluorescence.RNV was evaluated by paraffin sectioning and hematoxylin and eosin(HE)staining.Activation of retinal M uller glial cells were examined by immunoblot of glial fibrillary acidic protein(GFAP).rMC-1.a retinal Muller cell line,was used for in vitro study.Expression of hypoxia-induced factor 1α(HIF-1α)and vascular endothelial growth factor(VEGF)were determined by Western-blot analysis,enzyme-linked immunosorbent assay(ELISA)or immunostaining.RESULTS:Aberrant RNV and glial activation was observed after OIR.Of note,retinal AChE was mainly expressed by retinal Muller glial cells and markedly increased in OIR mice.Systemic administration of donepezil significantly reduced RNV and abnormal glial activation in mice with OIR.Moreover,ischemia-induced HIF-1αaccumulation and VEGF upregulation in OIR mouse retinas and cultured rMC-1 were significantly inhibited by donepezil intervention.CONCLUSION:AchE is implicated in RNV with OIR.Inhibition of AChE by donepeizl is likely to be a potential therapeutic approach for retinal neovascular diseases.