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学科主题: 临床医学
题名:
Ephrin-A2 and-A3 are negative regulators of the regenerative potential of Muller cells
作者: 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
发表日期: 2014-10-05
DOI: 10.3760/cma.j.issn.0366-6999.20141130
卷: 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
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
项目资助者: Department of Veterans Affairs ; Department of Defense ; Lion&prime ; s Foundation ; National Natural Science Foundation of China
WOS记录号: WOS:000344724000016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/49987
Appears in Collections:北京大学第一临床医学院_眼科_期刊论文

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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

Recommended Citation:
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.
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