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Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury.

Authors
  • Cheng, Lin1, 2
  • Wong, Lucy J2, 3
  • Yan, Naihong2, 4
  • Han, Richard C2
  • Yu, Honghua2
  • Guo, Chenying2
  • Batsuuri, Khulan2
  • Zinzuwadia, Aniket2
  • Guan, Ryan2
  • Cho, Kin-Sang2
  • Chen, Dong Feng2
  • 1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China. , (China)
  • 2 Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America. , (United States)
  • 3 Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. , (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. , (China)
Type
Published Article
Journal
PLoS ONE
Publisher
Public Library of Science
Publication Date
Jan 01, 2018
Volume
13
Issue
2
Identifiers
DOI: 10.1371/journal.pone.0191853
PMID: 29408885
Source
Medline
License
Unknown

Abstract

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.

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