{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T16:21:52Z","timestamp":1776010912647,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000738","name":"US Department of Veterans Affairs","doi-asserted-by":"crossref","award":["IK2BX002683"],"award-info":[{"award-number":["IK2BX002683"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH MSTP training","award":["T32 GM007250"],"award-info":[{"award-number":["T32 GM007250"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY025451"],"award-info":[{"award-number":["EY025451"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY027283"],"award-info":[{"award-number":["EY027283"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY009339"],"award-info":[{"award-number":["EY009339"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Age-related macular degeneration (AMD) is a chronic, multifactorial disorder and a leading cause of blindness in the elderly. Characterized by progressive photoreceptor degeneration in the central retina, disease progression involves epigenetic changes in chromatin accessibility resulting from environmental exposures and chronic stress. Here, we report that a photosensitive mouse model of acute stress-induced photoreceptor degeneration recapitulates the epigenetic hallmarks of human AMD. Global epigenomic profiling was accomplished by employing an Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq), which revealed an association between decreased chromatin accessibility and stress-induced photoreceptor cell death in our mouse model. The epigenomic changes induced by light damage include reduced euchromatin and increased heterochromatin abundance, resulting in transcriptional and translational dysregulation that ultimately drives photoreceptor apoptosis and an inflammatory reactive gliosis in the retina. Of particular interest, pharmacological inhibition of histone deacetylase 11 (HDAC11) and suppressor of variegation 3\u20139 homolog 2 (SUV39H2), key histone-modifying enzymes involved in promoting reduced chromatin accessibility, ameliorated light damage in our mouse model, supporting a causal link between decreased chromatin accessibility and photoreceptor degeneration, thereby elucidating a potential new therapeutic strategy to combat AMD.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa158","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T19:12:01Z","timestamp":1594926721000},"page":"2611-2624","source":"Crossref","is-referenced-by-count":14,"title":["Epigenetic hallmarks of age-related macular degeneration are recapitulated in a photosensitive mouse model"],"prefix":"10.1093","volume":"29","author":[{"given":"Jennings","family":"Luu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA"},{"name":"Gavin Herbert Eye Institute and the Department of Ophthalmology, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Les","family":"Kallestad","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute and the Department of Ophthalmology, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanh","family":"Hoang","sequence":"additional","affiliation":[{"name":"Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Lewandowski","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute and the Department of Ophthalmology, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqian","family":"Dong","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute and the Department of Ophthalmology, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seth","family":"Blackshaw","sequence":"additional","affiliation":[{"name":"Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA"},{"name":"Department of Ophthalmology, Department of Neurology, Center for Human Systems Biology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-545X","authenticated-orcid":false,"given":"Krzysztof","family":"Palczewski","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute and the Department of Ophthalmology, University of California-Irvine, Irvine, CA 92697, USA"},{"name":"Department of Physiology & Biophysics, School of Medicine, University of California-Irvine, Irvine, CA 92697, USA"},{"name":"Department of Chemistry, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"2020090402223612900_ref1","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1111\/j.1474-9726.2012.00835.x","article-title":"Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs","volume":"11","author":"Talens","year":"2012","journal-title":"Aging Cell"},{"key":"2020090402223612900_ref2","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/nature04844","article-title":"Increased cell-to-cell variation in gene expression in ageing mouse heart","volume":"441","author":"Bahar","year":"2006","journal-title":"Nature"},{"key":"2020090402223612900_ref3","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.cell.2012.01.003","article-title":"Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock","volume":"148","author":"Rando","year":"2012","journal-title":"Cell"},{"key":"2020090402223612900_ref4","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.cell.2007.01.029","article-title":"The epigenomics of cancer","volume":"128","author":"Jones","year":"2007","journal-title":"Cell"},{"key":"2020090402223612900_ref5","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/nrcardio.2010.104","article-title":"Epigenetics and cardiovascular disease","volume":"7","author":"Ordov\u00e1s","year":"2010","journal-title":"Nat. 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