机构：[1]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China,[2]Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America, [3]Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany[4]Department of Ophthalmology and Ophthalmic Laboratories, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China四川大学华西医院
Epigenetic predisposition is thought to critically contribute to adult-onset disorders, such as retinal neurodegeneration. The histone methyltransferase, enhancer of zeste homolog 2 (Ezh2), is transiently expressed in the perinatal retina, particularly enriched in retinal ganglion cells (RGCs). We previously showed that embryonic deletion of Ezh2 from retinal progenitors led to progressive photoreceptor degeneration throughout life, demonstrating a role for embryonic predisposition of Ezh2-mediated repressive mark in maintaining the survival and function of photoreceptors in the adult. Enrichment of Ezh2 in RGCs leads to the question if Ezh2 also mediates gene expression and function in postnatal RGCs, and if its deficiency changes RGC susceptibility to cell death under injury or disease in the adult. To test this, we generated mice carrying targeted deletion of Ezh2 from RGC progenitors driven by Math5-Cre (mKO). mKO mice showed no detectable defect in RGC development, survival, or cell homeostasis as determined by physiological analysis, live imaging, histology, and immunohistochemistry. Moreover, RGCs of Ezh2 deficient mice revealed similar susceptibility against glaucomatous and acute optic nerve trauma-induced neurodegeneration compared to littermate floxed or wild-type control mice. In agreement with the above findings, analysis of RNA sequencing of RGCs purified from Ezh2 deficient mice revealed few gene changes that were related to RGC development, survival and function. These results, together with our previous report, support a cell lineage-specific mechanism of Ezh2-mediated gene repression, especially those critically involved in cellular function and homeostasis.
基金：
This research was supported by funding
from the NIH/NEI (R41 EY025913 and
R01EY025259) and Curing Kids Fund to D.F.C.; the
Core Grant for Vision Research from NIH/NEI to
the Schepens Eye Research Institute
(P30EY03790), and the Postdoctoral Foundation to
L. C. (No. 2015M580758), the Natural Science Foundation of Guangdong Province
(2016A030310201) to L.C and Massachusetts
Lions Eye Research Fund to DFC. The funders did
not have any additional role in the study design,
data collection and analysis, decision to publish, or
preparation of the manuscript
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|3 区生物
小类|3 区综合性期刊
最新[2023]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
第一作者：
第一作者机构：[1]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China,[2]Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America,
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Cheng Lin,Wong Lucy J,Yan Naihong,et al.Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury.[J].PloS one.2018,13(2):e0191853.doi:10.1371/journal.pone.0191853.
APA：
Cheng Lin,Wong Lucy J,Yan Naihong,Han Richard C,Yu Honghua...&Chen Dong Feng.(2018).Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury..PloS one,13,(2)
MLA：
Cheng Lin,et al."Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury.".PloS one 13..2(2018):e0191853
