{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:52:14Z","timestamp":1785549134541,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008494","name":"Vontobel (Switzerland)","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100008494","id-type":"DOI","asserted-by":"publisher"}]},{"name":"OPOS Foundation (Switzerland)","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Forschungskredit of the University of Zurich","award":["FK-20-028"],"award-info":[{"award-number":["FK-20-028"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["31003A 122359"],"award-info":[{"award-number":["31003A 122359"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["31003A 173008"],"award-info":[{"award-number":["31003A 173008"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030 200798"],"award-info":[{"award-number":["310030 200798"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007214","name":"Velux Stiftung","doi-asserted-by":"publisher","award":["1371"],"award-info":[{"award-number":["1371"]}],"id":[{"id":"10.13039\/100007214","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","award":["016.Vici.170.024"],"award-info":[{"award-number":["016.Vici.170.024"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is a progressive disease of the macula characterized by atrophy of the retinal pigment epithelium (RPE) and photoreceptor degeneration, leading to severe vision loss at advanced stages in the elderly population. Impaired reverse cholesterol transport (RCT) as well as intracellular lipid accumulation in the RPE are implicated in AMD pathogenesis. Here, we focus on ATP-binding cassette transporter A1 (ABCA1), a major cholesterol transport protein in the RPE, and analyze conditions that lead to ABCA1 dysregulation in induced pluripotent stem cell (iPSC)-derived RPE cells (iRPEs). Our results indicate that the risk-conferring alleles rs1883025 (C) and rs2740488 (A) in ABCA1 are associated with increased ABCA1 mRNA and protein levels and reduced efficiency of cholesterol efflux from the RPE. Hypoxia, an environmental risk factor for AMD, reduced expression of ABCA1 and increased intracellular lipid accumulation. Treatment with a liver X receptor (LXR) agonist led to an increase in ABCA1 expression and reduced lipid accumulation. Our data strengthen the homeostatic role of cholesterol efflux in the RPE and suggest that increasing cellular cholesterol export by stimulating ABCA1 expression might lessen lipid load, improving RPE survival and reducing the risk of developing AMD.<\/jats:p>","DOI":"10.3390\/ijms23063194","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T22:09:58Z","timestamp":1647468598000},"page":"3194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Regulation of ABCA1 by AMD-Associated Genetic Variants and Hypoxia in iPSC-RPE"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8529-2326","authenticated-orcid":false,"given":"Florian","family":"Peters","sequence":"first","affiliation":[{"name":"Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, 8952 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9665-9197","authenticated-orcid":false,"given":"Lynn J. A.","family":"Ebner","sequence":"additional","affiliation":[{"name":"Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, 8952 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6537-8627","authenticated-orcid":false,"given":"David","family":"Atac","sequence":"additional","affiliation":[{"name":"Institute of Medical Molecular Genetics, University of Zurich, 8952 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-8739","authenticated-orcid":false,"given":"Jordi","family":"Maggi","sequence":"additional","affiliation":[{"name":"Institute of Medical Molecular Genetics, University of Zurich, 8952 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0370-3815","authenticated-orcid":false,"given":"Wolfgang","family":"Berger","sequence":"additional","affiliation":[{"name":"Institute of Medical Molecular Genetics, University of Zurich, 8952 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0634-5408","authenticated-orcid":false,"given":"Anneke I.","family":"den Hollander","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Radboud University Medical Center, 6525 Nijmegen, The Netherlands"},{"name":"AbbVie, Genomic Research Center, 200 Sidney Street, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-4352","authenticated-orcid":false,"given":"Christian","family":"Grimm","sequence":"additional","affiliation":[{"name":"Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, 8952 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. 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