April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Epigenetic repression of photoreceptor genes expression by Ezh2 is required for postnatal homeostasis
Naihong Yan; Lin Cheng; Honghua Yu; Kin-Sang Cho; Dongfeng Chen
Author Affiliations & Notes
  • Naihong Yan
    Department of Ophthalmology and Ophthalmic Laboratories, State Key Laboratory of Biotherapy,West China Hospital, Sichuan University, Chengdu, China
    Department of Ophthalmology, Schepens Eye Research Institute,Harvard Medical School, Boston, MA
  • Lin Cheng
    Department of Ophthalmology, Schepens Eye Research Institute,Harvard Medical School, Boston, MA
    Institute of Clinical Pharmacology, Central South University, Changsha, China
  • Honghua Yu
    Department of Ophthalmology, Schepens Eye Research Institute,Harvard Medical School, Boston, MA
  • Kin-Sang Cho
    Department of Ophthalmology, Schepens Eye Research Institute,Harvard Medical School, Boston, MA
  • Dongfeng Chen
    Department of Ophthalmology, Schepens Eye Research Institute,Harvard Medical School, Boston, MA
  • Footnotes
    Commercial Relationships Naihong Yan, None; Lin Cheng, None; Honghua Yu, None; Kin-Sang Cho, None; Dongfeng Chen, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4999. doi:
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      Naihong Yan, Lin Cheng, Honghua Yu, Kin-Sang Cho, Dongfeng Chen; Epigenetic repression of photoreceptor genes expression by Ezh2 is required for postnatal homeostasis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4999.

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Abstract

Purpose: To elucidate whether the polycomb histone methyltransferase Ezh2 regulates retinal neuron development and function.

Methods: The Ezh2 knockout mice line Chx10-cre Ezh2flox/flox was generated to investigate the roles of Ezh2 in retina development and function. The morphology of Chx10-cre Ezh2flox/flox and controls was detected by hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC). The thickness of retinal layers, mainly the outer nuclear layer (ONL) was measured with IHC and spectrum domain-OCT. Mouse retinal functions were assessed by electroretinogram (ERG) in animals aged 1- 12 months. The global gene expression profile of P0 Chx10-cre Ezh2flox/flox mice retina was examined by cDNA microarray, and the levels of expression of various retinal cell markerswere quantitatively assessed by real time RT-PCR. Bioinformatics and ChIP assay were employed to determine the downstream targets and signal events in Ezh2-deficient mice.

Results: The results of H&E, IHC and OCT showed that Chx10-cre Ezh2flox/flox mice exhibited progressive retina degeneration in the postnatal life. In Chx10-cre Ezh2flox/flox mice, retinal layers were substantially thinner than those of the littermate control retinas, and there was a progressive decrease of ONL in the Chx10-cre Ezh2flox/flox mouse retina from 1 - 12 month old. Chx10-cre Ezh2flox/flox mice also displayed progressive functional degeneration as measured by ERG. Significantly decreased ERG a and b wave amplitudes were observed between 1 to 12 month old Chx10-cre Ezh2flox/flox mice while their littermate control mice showed constant normal response of ERG a and b wave. Microarray and RT-PCR suggested that photoreceptor related genes (e.g., Recoverin and Rhodopsin) and the transcription factors Nrl were up-regulate in the retinas of Chx10-cre Ezh2flox/flox mice.

Conclusions: This study indicates that the H3K27me3 histone modification mediated by Ezh2 is essential for retinal development and homeostasis in the postnatal life.

Keywords: 695 retinal degenerations: cell biology • 533 gene/expression  
© 2014, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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