{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T05:34:35Z","timestamp":1788068075780,"version":"build-2784847793"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["U01EY034590 R01EY09076 5P30CA013696 U01EY030580 U54OD020351 R24EY028758 R24EY027285 5P30EY019"],"award-info":[{"award-number":["U01EY034590 R01EY09076 5P30CA013696 U01EY030580 U54OD020351 R24EY028758 R24EY027285 5P30EY019"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["5P30EY019007 R01EY018213 R01EY024698 R01EY026682 R21AG050437"],"award-info":[{"award-number":["5P30EY019007 R01EY018213 R01EY024698 R01EY026682 R21AG050437"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003194","name":"New York Stem Cell Foundation","doi-asserted-by":"publisher","award":["SDHDOH01-C32590GG-3450000"],"award-info":[{"award-number":["SDHDOH01-C32590GG-3450000"]}],"id":[{"id":"10.13039\/100003194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nancy & Kobi Karp","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Crowley Family Funds","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"The Rosenbaum Family Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100007817","name":"Novartis AG | Alcon | Alcon Research Institute","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007817","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gebroe Family Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["M2021002F"],"award-info":[{"award-number":["M2021002F"]}],"id":[{"id":"10.13039\/100006312","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":[[2023,5,9]]},"abstract":"<jats:p>\n                    Genome-wide association studies (GWAS) have identified genetic risk loci for age-related macular degeneration (AMD) on the chromosome 10q26 (Chr10) locus and are tightly linked: the A69S (G&gt;T) rs10490924 single-nucleotide variant (SNV) and the AATAA-rich insertion\u2013deletion (indel, del443\/ins54), which are found in the age-related maculopathy susceptibility 2 (\n                    <jats:italic>ARMS2<\/jats:italic>\n                    ) gene, and the G512A (G&gt;A) rs11200638 SNV, which is found in the\u00a0high-temperature requirement A serine peptidase 1\u00a0(\n                    <jats:italic>HTRA1<\/jats:italic>\n                    ) promoter. The fourth variant is Y402H complement factor H (\n                    <jats:italic>CFH<\/jats:italic>\n                    ), which directs\n                    <jats:italic>CFH<\/jats:italic>\n                    \u00a0signaling. CRISPR manipulation of retinal pigment epithelium (RPE) cells may allow one to isolate the effects of the individual SNV and thus identify SNV-specific effects on cell phenotype. Clustered regularly interspaced short palindromic repeats (CRISPR) editing demonstrates that rs10490924 raised oxidative stress in induced pluripotent stem cell (iPSC)-derived retinal cells from patients with AMD. Sodium phenylbutyrate preferentially reverses the cell death caused by\n                    <jats:italic>ARMS2<\/jats:italic>\n                    rs10490924 but not\n                    <jats:italic>HTRA1<\/jats:italic>\n                    rs11200638. This study serves as a proof of concept for the use of patient-specific iPSCs for functional annotation of tightly linked GWAS to study the etiology of a late-onset disease phenotype. More importantly, we demonstrate that antioxidant administration may be useful for reducing reactive oxidative stress in AMD, a prevalent late-onset neurodegenerative disorder.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2215005120","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T15:11:27Z","timestamp":1682953887000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":15,"title":["CRISPR editing demonstrates rs10490924 raised oxidative stress in iPSC-derived retinal cells from patients with\n                    <i>ARMS2\/HTRA1<\/i>\n                    -related AMD"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9704-5448","authenticated-orcid":false,"given":"Ya-Ju","family":"Chang","sequence":"first","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura\u00a0A.","family":"Jenny","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Shi","family":"Li","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Cui","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3925-5572","authenticated-orcid":false,"given":"Yang","family":"Kong","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Li","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7448-5950","authenticated-orcid":false,"given":"Janet\u00a0R.","family":"Sparrow","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY 10032"},{"name":"Department of Ophthalmology, Columbia University, New York, NY 10032"},{"name":"Department of Biomedical Engineering, Columbia University, New York, NY 10032"},{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen\u00a0H.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Department of Ophthalmology, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY 10032"},{"name":"Department of Ophthalmology, Columbia University, New York, NY 10032"},{"name":"Department of Biomedical Engineering, Columbia University, New York, NY 10032"},{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY 10032"},{"name":"Institute of Human Nutrition, and Columbia Stem Cell Initiative, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu053"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2007.10.032"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-010-0805-8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/444437"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.24546"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0190-15.2015"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.07.017"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0344"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","unstructured":"F. 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NCBI dbGAP. http:\/\/www.ncbi.nlm.nih.gov\/projects\/gap\/cgi-bin\/study.cgi?study_id=phs003276.v1.p1. Deposited 20 April 2023."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2215005120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:18:59Z","timestamp":1695287939000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2215005120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":34,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2023,5,9]]}},"alternative-id":["10.1073\/pnas.2215005120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2215005120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5]]},"assertion":[{"value":"2022-09-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2215005120"}}