{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:44Z","timestamp":1792787624967,"version":"4.5.0"},"reference-count":84,"publisher":"American Society for Clinical Investigation","issue":"1","funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01 EY027802,R01 EY028160"],"award-info":[{"award-number":["R01 EY027802,R01 EY028160"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["P30 EY005722"],"award-info":[{"award-number":["P30 EY005722"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["P30 EY000331"],"award-info":[{"award-number":["P30 EY000331"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01 EY019287-06"],"award-info":[{"award-number":["R01 EY019287-06"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["P30 EY02687"],"award-info":[{"award-number":["P30 EY02687"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01 EY027691"],"award-info":[{"award-number":["R01 EY027691"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008097","name":"Edward N. and Della L. Thome Memorial Foundation","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100008097","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010657","name":"Carl Marshall and Mildred Almen Reeves Foundation","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100010657","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009784","name":"Starr Foundation","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100009784","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Bill and Emily Kuzma Family Gift for Retinal Research","award":["None"],"award-info":[{"award-number":["None"]}]},{"name":"Jeffrey Fort Innovation Fund","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100001642","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Thome Foundation","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,16]]},"abstract":"<jats:p>\n                    Effective treatments and animal models for the most prevalent neurodegenerative form of blindness in elderly people, called age-related macular degeneration (AMD), are lacking. Genome-wide association studies have identified lipid metabolism and inflammation as AMD-associated pathogenic pathways. Given liver X receptors (LXRs), encoded by the nuclear receptor subfamily 1 group H members 2 and 3 (\n                    <jats:italic>NR1H3<\/jats:italic>\n                    and\n                    <jats:italic>NR1H2<\/jats:italic>\n                    ), are master regulators of these pathways, herein we investigated the role of LXR in human and mouse eyes as a function of age and disease and tested the therapeutic potential of targeting LXR. We identified immunopositive LXR fragments in human extracellular early dry AMD lesions and a decrease in LXR expression within the retinal pigment epithelium (RPE) as a function of age. Aged mice lacking\n                    <jats:italic>LXR<\/jats:italic>\n                    presented with isoform-dependent ocular pathologies. Specifically, loss of the\n                    <jats:italic>Nr1h3<\/jats:italic>\n                    isoform resulted in pathobiologies aligned with AMD, supported by compromised visual function, accumulation of native and oxidized lipids in the outer retina, and upregulation of ocular inflammatory cytokines, while absence of\n                    <jats:italic>Nr1h2<\/jats:italic>\n                    was associated with ocular lipoidal degeneration. LXR activation not only ameliorated lipid accumulation and oxidant-induced injury in RPE cells but also decreased ocular inflammatory markers and lipid deposition in a mouse model, thereby providing\ufeff translational support for pursuing LXR-active pharmaceuticals as potential therapies for dry AMD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.131928","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T12:00:44Z","timestamp":1576152044000},"source":"Crossref","is-referenced-by-count":57,"title":["LXRs regulate features of age-related macular degeneration and may be a potential therapeutic target"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8056-011X","authenticated-orcid":true,"given":"Mayur","family":"Choudhary","sequence":"first","affiliation":[{"name":"Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebraheim N.","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-7194","authenticated-orcid":true,"given":"Pei-Li","family":"Yao","sequence":"additional","affiliation":[{"name":"Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faryan","family":"Tayyari","sequence":"additional","affiliation":[{"name":"Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5064-6403","authenticated-orcid":true,"given":"Roxana A.","family":"Radu","sequence":"additional","affiliation":[{"name":"Stein Eye Institute, Department of Ophthalmology, UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Nusinowitz","sequence":"additional","affiliation":[{"name":"Stein Eye Institute, Department of Ophthalmology, UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0796-1766","authenticated-orcid":true,"given":"Michael E.","family":"Boulton","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra S.","family":"Apte","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Ruberti","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Handa","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1259-0477","authenticated-orcid":true,"given":"Peter","family":"Tontonoz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goldis","family":"Malek","sequence":"additional","affiliation":[{"name":"Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA."},{"name":"Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.17925\/USOR.2017.10.02.119"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(13)70145-1"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6476"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2004.09.017"},{"issue":"Pt 3","key":"B5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/eye.1994.57","article-title":"Evolution of soft drusen in age-related macular degeneration","volume":"8","author":"Sarks","year":"1994","journal-title":"Eye (Lond)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6701978"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1121"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110359"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3448"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.11.016"},{"issue":"47","key":"B11","doi-asserted-by":"crossref","DOI":"10.1126\/sageke.2004.47.re8","article-title":"Nuclear hormone receptors, metabolism, and aging: what goes around comes around. Transcription factors link lipid metabolism and aging-related processes","volume":"2004","author":"Pardee","year":"2004","journal-title":"Sci Aging Knowledge Environ"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R075556"},{"issue":"Pt A","key":"B13","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.nbd.2014.05.019","article-title":"Nuclear receptors in neurodegenerative diseases","volume":"72","author":"Skerrett","year":"2014","journal-title":"Neurobiol Dis"},{"key":"B14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.21775\/cimb.022.041","article-title":"Liver X Receptors and their agonists: targeting for cholesterol homeostasis and cardiovascular diseases","volume":"22","author":"Ma","year":"2017","journal-title":"Curr Issues Mol Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2017.102"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0392"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.191197"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27883"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1709-x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912702107"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912019107"},{"issue":"4","key":"B22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S1537-1891(02)00175-1","article-title":"LXRs; oxysterol-activated nuclear receptors that regulate genes controlling lipid homeostasis","volume":"38","author":"Edwards","year":"2002","journal-title":"Vascul Pharmacol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.13.6393"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15195"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(00)00140-5"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-007-9064-y"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(81)90234-8"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-25786"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.08.001"},{"key":"B30","doi-asserted-by":"crossref","DOI":"10.1155\/2011\/802059","article-title":"Lipids, lipoproteins, and age-related macular degeneration","volume":"2011","author":"Ebrahimi","year":"2011","journal-title":"J Lipids"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1086\/301901"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00961-2"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61872-5"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2017.06.013"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0496"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2007.03.011"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nm820"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nri3459"},{"issue":"1","key":"B39","first-page":"265","article-title":"Accumulation of cholesterol with age in human Bruch\u2019s membrane","volume":"42","author":"Curcio","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2009.953448"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2011-300344"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0034"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63836-9"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R002238"},{"issue":"3","key":"B45","doi-asserted-by":"crossref","DOI":"10.1095\/biolreprod.115.133538","article-title":"Liver X receptors (LXRs) alpha and beta play distinct roles in the mouse epididymis","volume":"94","author":"Whitfield","year":"2016","journal-title":"Biol Reprod"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81432-4"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9794"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80736-E"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.03.002"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6021"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.744656"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2008.08.010"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2016.07.013"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1080\/02713680701550660"},{"key":"B55","article-title":"Liver X receptor \u03b1 is essential for the capillarization of liver sinusoidal endothelial cells in liver injury","volume":"6","author":"Xing","year":"2016","journal-title":"Sci Rep"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15612"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7782"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3383"},{"issue":"4","key":"B59","first-page":"535","article-title":"Interleukin-13 and age-related macular degeneration","volume":"10","author":"Fu","year":"2017","journal-title":"Int J Ophthalmol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.2741\/2853"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-9165"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080350"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60363"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1596"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.07.053"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-017-1036-4"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.07.007"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.03.047"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06471.x"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-013-8461-3"},{"issue":"1","key":"B71","doi-asserted-by":"crossref","DOI":"10.3390\/molecules22010088","article-title":"Ligands of therapeutic utility for the liver X receptors","volume":"22","author":"Komati","year":"2017","journal-title":"Molecules"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2008.09.001"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.05.012"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5429"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6163"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1021\/pr1008898"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63816"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02183.x"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053529"},{"key":"B80","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.45100","article-title":"Impaired ABCA1\/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration","volume":"8","author":"Storti","year":"2019","journal-title":"Elife"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M084442"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1904719116"},{"issue":"17","key":"B83","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.120824","article-title":"Impaired monocyte cholesterol clearance initiates age-related retinal degeneration and vision loss","volume":"3","author":"Ban","year":"2018","journal-title":"JCI Insight"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R010538"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/131928\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:19:35Z","timestamp":1779193175000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/131928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,16]]},"references-count":84,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1,16]]},"published-print":{"date-parts":[[2020,1,16]]}},"alternative-id":["10.1172\/jci.insight.131928"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.131928","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,16]]},"article-number":"e131928"}}