{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T11:11:50Z","timestamp":1776510710875,"version":"3.51.2"},"reference-count":73,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EY30141 (RK)"],"award-info":[{"award-number":["R01 EY30141 (RK)"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL129051 (STR)"],"award-info":[{"award-number":["R01 HL129051 (STR)"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NEI EY00331-43"],"award-info":[{"award-number":["NEI EY00331-43"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["6009"],"award-info":[{"award-number":["6009"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["60060B"],"award-info":[{"award-number":["60060B"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jules Stein Eye Institute Core Grant for Vision Research","award":["R01 EY30141 (RK)"],"award-info":[{"award-number":["R01 EY30141 (RK)"]}]},{"name":"Jules Stein Eye Institute Core Grant for Vision Research","award":["R01 HL129051 (STR)"],"award-info":[{"award-number":["R01 HL129051 (STR)"]}]},{"name":"Jules Stein Eye Institute Core Grant for Vision Research","award":["NEI EY00331-43"],"award-info":[{"award-number":["NEI EY00331-43"]}]},{"name":"Jules Stein Eye Institute Core Grant for Vision Research","award":["6009"],"award-info":[{"award-number":["6009"]}]},{"name":"Jules Stein Eye Institute Core Grant for Vision Research","award":["60060B"],"award-info":[{"award-number":["60060B"]}]},{"name":"Ryan Initiative for Macular Research (RIMR)","award":["R01 EY30141 (RK)"],"award-info":[{"award-number":["R01 EY30141 (RK)"]}]},{"name":"Ryan Initiative for Macular Research (RIMR)","award":["R01 HL129051 (STR)"],"award-info":[{"award-number":["R01 HL129051 (STR)"]}]},{"name":"Ryan Initiative for Macular Research (RIMR)","award":["NEI EY00331-43"],"award-info":[{"award-number":["NEI EY00331-43"]}]},{"name":"Ryan Initiative for Macular Research (RIMR)","award":["6009"],"award-info":[{"award-number":["6009"]}]},{"name":"Ryan Initiative for Macular Research (RIMR)","award":["60060B"],"award-info":[{"award-number":["60060B"]}]},{"name":"KECK Foundation to Doheny Eye Institute","award":["R01 EY30141 (RK)"],"award-info":[{"award-number":["R01 EY30141 (RK)"]}]},{"name":"KECK Foundation to Doheny Eye Institute","award":["R01 HL129051 (STR)"],"award-info":[{"award-number":["R01 HL129051 (STR)"]}]},{"name":"KECK Foundation to Doheny Eye Institute","award":["NEI EY00331-43"],"award-info":[{"award-number":["NEI EY00331-43"]}]},{"name":"KECK Foundation to Doheny Eye Institute","award":["6009"],"award-info":[{"award-number":["6009"]}]},{"name":"KECK Foundation to Doheny Eye Institute","award":["60060B"],"award-info":[{"award-number":["60060B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lipid peroxidation from oxidative stress is considered a major contributor to age-related macular degeneration (AMD). The retina is abundant with circulating low-density lipoproteins (LDL), which are taken up by LDL receptor (LDLR) in the RPE and M\u00fcller cells. The purpose of this study is to investigate the role of LDLR in the NaIO3-induced model of dry AMD. Confluent primary human RPE (hRPE) and LDLR-silenced ARPE-19 cells were stressed with 150 \u00b5M tert-butyl hydroperoxide (tBH) and caspase 3\/7 activation was determined. WT and Ldlr\u2212\/\u2212 mice were administered NaIO3 (20 mg\/kg) intravenously. On day 7, fundus imaging, OCT, ERG, and retinal thickness were measured. Histology, TUNEL, cleaved caspase 3 and lipid accumulation were assessed. Treatment of hRPE with tBH markedly decreased LDLR expression. Caspase 3\/7 activation was significantly increased in LDLR-silenced ARPE-19 cells treated with tBH. In Ldlr\u2212\/\u2212 mice, NaIO3 administration resulted in significant (a) retinal thinning, (b) compromised photoreceptor function, (c) increased percentage of cleaved caspase 3 positive and apoptotic cells, and (d) increased lipid droplet accumulation in the RPE, Bruch membrane, choroid, and sclera, compared to WT mice. Our findings imply that LDLR loss leads to lipid accumulation and impaired retinal function, which may contribute to the development of AMD.<\/jats:p>","DOI":"10.3390\/cells12010043","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T03:02:15Z","timestamp":1671764535000},"page":"43","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Oxidative Stress and Lipid Accumulation Augments Cell Death in LDLR-Deficient RPE Cells and Ldlr\u2212\/\u2212 Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9425-3986","authenticated-orcid":false,"given":"Parameswaran Gangadharan","family":"Sreekumar","sequence":"first","affiliation":[{"name":"Doheny Eye Institute, Pasadena, CA 91103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0509-6764","authenticated-orcid":false,"given":"Feng","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Spee","sequence":"additional","affiliation":[{"name":"Doheny Eye Institute, Pasadena, CA 91103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Araujo","sequence":"additional","affiliation":[{"name":"Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Nusinowitz","sequence":"additional","affiliation":[{"name":"Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-9531","authenticated-orcid":false,"given":"Srinivasa T","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram","family":"Kannan","sequence":"additional","affiliation":[{"name":"Doheny Eye Institute, Pasadena, CA 91103, USA"},{"name":"Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. 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