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Ephrin-A2 and-A3 are negative regulators of the regenerative potential of Muller cells
Zhu Ruilin1,2,3; Cho Kin-Sang3; Chen Dong Feng3,4; Yang Liu1,2
关键词Muller Cell Stem Cell Retinal Regeneration
刊名CHINESE MEDICAL JOURNAL
2014-10-05
DOI10.3760/cma.j.issn.0366-6999.20141130
127期:19页:3438-3442
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
资助者Department of Veterans Affairs ; Department of Defense ; Lion&prime ; s Foundation ; National Natural Science Foundation of China ; Department of Veterans Affairs ; Department of Defense ; Lion&prime ; s Foundation ; National Natural Science Foundation of China
研究领域[WOS]General & Internal Medicine
关键词[WOS]RETINAL STEM-CELLS ; NEURAL REGENERATION ; PROLIFERATION ; GLIA ; NEUROGENESIS ; SURVIVAL ; RECEPTOR ; INJURY ; EYE
英文摘要

Background In a previous study, we demonstrated that ephrin-A2 and -A3 negatively regulate the growth of neural progenitor cells in the central nervous system. Adult mice deficient in ephrin-A2 and -A3 (A2(-/-)A3(-/-)) displayed active ongoing neurogenesis throughout the brain, and mice deficient in ephrin-A3 alone showed increased proliferation of ciliary epithelium derived retinal stem cells. This study aimed to detect that the increase in proliferation and neurogenic potential of Muller cells is influenced by the absence of ephrin-A2 and -A3.

Methods We assessed the retinal and Muller cell expression of ephrin-As and their receptor and neural progenitor cell markers by immunostaining and real-time PCR. We cultured purified primary Muller cells derived from wild-type and A2(-/-)A3(-/-) mice in a defined culture medium that enables trans-differentiation of Muller cells into retinal neurons. To evaluate proliferating Muller cells in vivo, we injected 5′-ethylnyl-2′-deoxiuridine (EdU) intraperitoneally to adult mice.

Results Expression of ephrin-A2/A3 and their receptor EphA4 were detected in the retinas of adult mice, with EphA4 expression particularly enriched in Muller cells. Muller cells of A2(-/-)A3(-/-) mice exhibited significantly elevated expression of retinal progenitor cell markers, Pax6 and Chx10, when compared with those from wild-type mice. Moreover, a higher percentage of Muller cells of A2(-/-)A3(-/-) mice trans-differentiated and became recoverin+ and beta-III-tublin+ in the culture than those from wild type mice. Strikingly, an increased number of EdU+ retinal cells was detected in the retinas of adult A2(-/-)A3(-/-) mice as compared with wild-type mice.

Conclusions Ephrin-A2 and -A3 are negative regulators of the proliferative and neurogenic potentials of Muller cells. Manipulating ephrin-A signaling may thus represent a novel strategy for stimulating neuroregeneration from endogenous progenitors to participate in retinal repair in case of disease or damage.

语种英语
所属项目编号1I01RX000110 ; W81XWH-09-2-0091 ; 81170837
资助者Department of Veterans Affairs ; Department of Defense ; Lion&prime ; s Foundation ; National Natural Science Foundation of China ; Department of Veterans Affairs ; Department of Defense ; Lion&prime ; s Foundation ; National Natural Science Foundation of China
WOS记录号WOS:000344724000016
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/49987
专题北京大学第一临床医学院_眼科
作者单位1.Peking Univ, Dept Ophthalmol, Hosp 1, Beijing 100034, Peoples R China
2.Minist Educ, Key Lab Vis Loss & Restorat, Beijing 100034, Peoples R China
3.Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear, Boston, MA USA
4.Boston VA Healthcare Syst, Boston, MA USA
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GB/T 7714
Zhu Ruilin,Cho Kin-Sang,Chen Dong Feng,et al. Ephrin-A2 and-A3 are negative regulators of the regenerative potential of Muller cells[J]. CHINESE MEDICAL JOURNAL,2014,127(19):3438-3442.
APA Zhu Ruilin,Cho Kin-Sang,Chen Dong Feng,&Yang Liu.(2014).Ephrin-A2 and-A3 are negative regulators of the regenerative potential of Muller cells.CHINESE MEDICAL JOURNAL,127(19),3438-3442.
MLA Zhu Ruilin,et al."Ephrin-A2 and-A3 are negative regulators of the regenerative potential of Muller cells".CHINESE MEDICAL JOURNAL 127.19(2014):3438-3442.
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