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Lili Gong, Ruili Qi, Qian Sun, Fang-yuan liu, Zhong-wen Luo, QIAN Nie, Xiao-Dong Gong, Yun-Fei Liu, Lan Zhang, Xiangcheng Tang, Yizhi Liu, David W Li; Heterochromatin Protects Retinal Pigment Epithelial Cells from Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3561.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress (OS)-induced retinal pigment epithelium (RPE) cell apoptosis is critically implicated in the pathogenesis of age-related macular degeneration (AMD), one of the leading causes for blindness in the elderly. The highly condensed, repressive heterochromatin is recently found to paly critical roles in mediating diverse stress response. How RPE heterochromatin is regulated upon OS exposure remains elusive. This study is aimed to investigate heterochromatin structures and functions upon OS exposure.
We used a mouse model and cultured human RPE cells to investigate heterochromatin upon OS exposure. Oxidative stress was generated by retro-obital injection of sodium iodate (70 mg/kg) in mice or exposure of glucose oxidase (10 U/ml) in RPE cells. The heterochromatin status was assessed by micrococcal nuclease digestion, immunofluorescence microscopy, western blot, quantitative RT-PCR and chromatin immunoprecipitation analysis. To determine the biological functions of heterochromatin in OS, both pharmaceutical and genetic approaches were applied. MTT assay, flow cytometry and permeability measurement were employed to determine the RPE cell viability, apoptosis and barrier functions, respectively.
OS led to increase heterochromatin formation, as indicated by upregulation of trimethylation at histone3 lyscine9 (H3K9me3) and suppression of heterochromatin satellite genes. Disruption of heterochromatin by chaetocin, a selective inhibitor of H3K9 methyltransferases SUV39H1, led to increased cell apoptosis and degeneration of RPE upon OS exposure. Enhance heterochromatin formation by resveratrol treatment or overexpression of SUV39H1 increased cell viability in oxidative injury.
Heterochromatin protects RPE cells from OS-induced cell damage. Targeting heterochromatin may provide a potential strategy for AMD treatment.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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