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Absence of ephrin-a2/A3 increases retinal regenerative potential for Müller cells in Rhodopsin knockout mice

Neural Regeneration Research 2021年第7期16卷 1317-1322页

作者： Rui-Lin Zhu Yuan Fang Hong-Hua Yu Dong FChen Liu Yang Kin-Sang Cho Department of Ophthalmology Peking University First HospitalBeijingChina Schepens Eye Research Institute Massachusetts Eye and EarHarvard Medical SchoolBostonMAUSA Department of Ophthalmology and Visual Science Eye&ENT HospitalShanghai Medical CollegeFudan UniversityShanghaiChina Guangdong Eye Institute Department of OphthalmologyGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong ProvinceChina

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

关键词： endogenous stem cell EphA4 ephrin-a2 ephrin-A3 ephrins Müller cell photoreceptor cell regeneration retinal degeneration retinal regeneration retinal stem cell

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