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 

机构地区：[1]Department of Ophthalmology,Peking University First Hospital,Beijing,China [2]Schepens Eye Research Institute,Massachusetts Eye and Ear,Harvard Medical School,Boston,MA,USA [3]Department of Ophthalmology and Visual Science,Eye&ENT Hospital,Shanghai Medical College,Fudan University,Shanghai,China [4]Guangdong Eye Institute,Department of Ophthalmology,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou,Guangdong Province,China

出　　处：《Neural Regeneration Research》2021年第7期1317-1322,共6页中国神经再生研究（英文版）

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)。

摘　　要：Müller cells(MC) are considered dormant retinal progenitor cells in mammals.Previous studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and brain.It remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of MC.Here we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Müller cells.In this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in MC.The level of ephrin As/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of MC.Next, we investigated the proliferation in primary MC cultures isolated from wild-type and A2~(–/–) A3~(–/–) mice by 5-ethynyl-2′-deoxyuridine(EdU) incorporation.We detected a significant increase of EdU~+ cells in MC derived from A2~(–/–) A3~(–/–) mice.Next, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout(Rho~(–/–)) mice.To 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 retina.Ephrin As/EphA4 expression was upregulated in the retina of Rho~(–/–) mice compared to the wild-type mice.In 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 mice.Interestingly, 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 prolifera

关 键 词：endogenous stem cell EphA4 ephrin-A2 ephrin-A3 EPHRINS Müller cell photoreceptor cell regeneration retinal degeneration retinal regeneration retinal stem cell 

分 类 号：R459.9[医药卫生—治疗学] R364[医药卫生—临床医学]