A widespread decrease of chromatin accessibility in age-related macular degeneration

Jie Wang, Cristina Zibetti, Peng Shang, Srinivasa R. Sripathi, Pingwu Zhang, Marisol Cano, Thanh Hoang, Shuli Xia, Hongkai Ji, Shannath L. Merbs, Donald J. Zack, James T. Handa, Debasish Sinha, Seth Blackshaw, Jiang Qian

Research output: Contribution to journalArticlepeer-review

Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profiled chromatin accessibility in the retina and retinal pigmented epithelium (RPE) from AMD patients and controls. Global decreases in chromatin accessibility occurr in RPE in early AMD, and in the retina with advanced disease, suggesting that dysfunction in RPE cells drives disease progression. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates epigenomic changes seen in AMD, providing an epigenetic link between the known risk factors for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the reduction in chromatin accessibility, identifying potential new targets for treatment of AMD.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Feb 13 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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