{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:59:25Z","timestamp":1790913565404,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"31","license":[{"start":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T00:00:00Z","timestamp":1484697600000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.pnas.org\/preview_site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["R01EY023299"],"award-info":[{"award-number":["R01EY023299"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["M2015350"],"award-info":[{"award-number":["M2015350"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted grant"],"award-info":[{"award-number":["Unrestricted grant"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,8,2]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The complement system regulates immune defense and inflammation. Abnormal complement activation in the retina is associated with blinding macular degenerations, which have limited treatment options. The retinal pigment epithelium (RPE) is an initial site of injury in macular degenerations, but mechanisms that protect the RPE from complement-mediated damage are unclear. Here, we identify two critical responses to complement in the RPE: accelerated recycling of the complement inhibitor CD59 and lysosome-mediated membrane repair. We show that in models of macular degeneration, excess cholesterol impairs both defense mechanisms, resulting in mitochondrial damage. Drugs that decrease RPE cholesterol restore these mechanisms and help the RPE combat complement attack. Our studies identify promising drug targets to preserve RPE health and function in macular degenerations.<\/jats:p>","DOI":"10.1073\/pnas.1523061113","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T22:18:28Z","timestamp":1468880308000},"page":"8789-8794","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Protective responses to sublytic complement in the retinal pigment epithelium"],"prefix":"10.1073","volume":"113","author":[{"given":"Li Xuan","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706;"},{"name":"Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, WI 53706;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Toops","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706;"},{"name":"McPherson Eye Research Institute, University of Wisconsin, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Lakkaraju","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706;"},{"name":"Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, WI 53706;"},{"name":"McPherson Eye Research Institute, University of Wisconsin, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,7,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.04.003"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2015.02.032"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.03.007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-12757"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-009-8146-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201410112"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1506960112"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.191866"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604255103"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121309109"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500937"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.214593"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.11.003"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-3209-8_34"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi500157z"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4128"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.11.005"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10449"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab1482"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e14-05-1028"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702504104"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1309"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.001"},{"key":"e_1_3_3_24_2","first-page":"2903","article-title":"The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation","volume":"126","author":"Triantafilou K","year":"2013","unstructured":"K Triantafilou, TR Hughes, M Triantafilou, BP Morgan, The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation. J Cell Sci 126, 2903\u20132913 (2013).","journal-title":"J Cell Sci"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.109421"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-12-0730"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1656-2"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200208154"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.07.008"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-08-0707"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-014126"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200811005"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-03-0193"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200677200"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-11688"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808166200"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71029"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.05.003"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1523061113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1523061113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:51:31Z","timestamp":1649814691000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1523061113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,18]]},"references-count":38,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2016,8,2]]}},"alternative-id":["10.1073\/pnas.1523061113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1523061113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,18]]},"assertion":[{"value":"2016-07-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}