Absence of ephrin-A2/A3 increases retinal regenerative potential for Müller cells in Rhodopsin knockout mice

作     者：Rui-Lin Zhu Yuan Fang Hong-Hua Yu Dong FChen Liu Yang Kin-Sang Cho Rui-Lin Zhu;Yuan Fang;Hong-Hua Yu;Dong F.Chen;Liu Yang;Kin-Sang Cho

作者机构：Department of OphthalmologyPeking University First HospitalBeijingChina Schepens Eye Research InstituteMassachusetts Eye and EarHarvard Medical SchoolBostonMAUSA Department of Ophthalmology and Visual ScienceEye&ENT HospitalShanghai Medical CollegeFudan UniversityShanghaiChina Guangdong Eye InstituteDepartment of OphthalmologyGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2021年第16卷第7期

页      面：1317-1322页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 1010[医学-医学技术（可授医学、理学学位）] 100104[医学-病理学与病理生理学] 100215[医学-康复医学与理疗学] 10[医学] 

基　　金：supported by the grants from Lion's Foundation Grant and Bright Focus Foundation(to KSC) the National Natural Science Foundation of China, No.81600727(to RLZ) 

主　　题：endogenous stem cell EphA4 ephrin-A2 ephrin-A3 ephrins Müller cell photoreceptor cell regeneration retinal degeneration retinal regeneration retinal stem cell 

摘      要：Müller cells(MC) are considered dormant retinal progenitor cells in *** studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and *** remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of *** we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Müller *** this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in *** level of ephrin As/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of ***, we investigated the proliferation in primary MC cultures isolated from wild-type and A2~(–/–) A3~(–/–) mice by 5-ethynyl-2′-deoxyuridine(EdU) *** detected a significant increase of EdU~+ cells in MC derived from A2~(–/–) A3~(–/–) ***, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout(Rho~(–/–)) *** further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2~(–/–) A3~(–/–), Rho~(–/–) and Rho~(–/–) A2~(–/–) A3~(–/–) mice and the numbers of EdU~+ cells distributed among different layers of the *** As/EphA4 expression was upregulated in the retina of Rho~(–/–) mice compared to the wild-type *** addition, cultured MC derived from ephrin-A2~(–/–) A3~(–/–) mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type ***, we detected a significant increase of EdU~+ cells in the retinas of adult ephrin-A2~(–/–) A3~(–/–) mice mainly in the inner nuclear layer;and these EdU~+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from