@article {303901,
	title = {Ephrin-A2 and -A3 are negative regulators of the regenerative potential of M{\"o}ller cells},
	journal = {Chin Med J (Engl)},
	volume = {127},
	number = {19},
	year = {2014},
	month = {2014},
	pages = {3438-42},
	abstract = {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 M{\"u}ller cells is influenced by the absence of ephrin-A2 and -A3. METHODS: We assessed the retinal and M{\"u}ller cell expression of ephrin-As and their receptor and neural progenitor cell markers by immunostaining and real-time PCR. We cultured purified primary M{\"u}ller cells derived from wild-type and A2(-/-)A3(-/-) mice in a defined culture medium that enables trans-differentiation of M{\"u}ller cells into retinal neurons. To evaluate proliferating M{\"u}ller cells in vivo, we injected 5{\textquoteright}-ethylnyl-2{\textquoteright}-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 M{\"u}ller cells. M{\"u}ller 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 M{\"u}ller cells of A2(-/-)A3(-/-) mice trans-differentiated and became recoverin+ and β-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 M{\"u}ller 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.},
	keywords = {Animals, Cell Differentiation, Ephrin-A2, Ephrin-A3, Fluorescent Antibody Technique, Mice, Mice, Inbred C57BL, Mice, Knockout, Real-Time Polymerase Chain Reaction, Receptor, EphA4, Retina, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells},
	issn = {0366-6999},
	author = {Zhu, Ruilin and Cho, Kin-Sang and Chen, Dong Feng and Yang, Liu}
}
