{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T01:05:54Z","timestamp":1783386354600,"version":"3.54.6"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH 5P20GM121325 COBRE"],"award-info":[{"award-number":["NIH 5P20GM121325 COBRE"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R16GM154726"],"award-info":[{"award-number":["R16GM154726"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH 1R01EY031594\u201001A1"],"award-info":[{"award-number":["NIH 1R01EY031594\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH 1R01EY032516\u201001A1"],"award-info":[{"award-number":["NIH 1R01EY032516\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH K99EY033421"],"award-info":[{"award-number":["NIH K99EY033421"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY001765"],"award-info":[{"award-number":["EY001765"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Age\u2010related macular degeneration (AMD), a leading cause of vision loss affecting retinal pigment epithelial (RPE) cells, remains largely unexplained by current genome\u2010wide association studies (GWAS) risk variants. Our research on\n                    <jats:italic>Cryba1<\/jats:italic>\n                    , encoding \u03b2A3\/A1\u2010crystallin protein, reveals its crucial role in RPE cell function via a novel epigenetic mechanism, also evident in human atrophic AMD samples. Loss of\n                    <jats:italic>Cryba1<\/jats:italic>\n                    in mouse RPE cells triggers epigenetic changes by reducing histone deacetylase 3 (HDAC3) activity through two mechanisms. First,\n                    <jats:italic>Cryba1<\/jats:italic>\n                    depletion reduces inositol polyphosphate multikinase (IPMK) expression, which potentially reduces inositol hexakisphosphate (InsP6) generation since IPMK's kinase activity is essential for producing InsP4 and InsP5 as precursors to InsP6. Since InsP4, InsP5, or InsP6 is crucial for HDAC3's interaction with the corepressor's DAD domains, reduced IPMK expression in\n                    <jats:italic>Cryba1<\/jats:italic>\n                    \u2010depleted cells likely diminishes the HDAC3\u2010DAD interaction, leading to a reduction in HDAC3's activity. Second, reduced \u03b2A3\/A1 protein in\n                    <jats:italic>Cryba1<\/jats:italic>\n                    \u2010deficient cells impairs HDAC3's interaction with casein kinase 2 (CK2), resulting in decreased HDAC3 phosphorylation. Collectively, this increases H3K27 acetylation at the RET promoter region, likely enhancing the transcription of RET, a receptor tyrosine kinase critical for cell survival. Although RET is transcriptionally increased,\n                    <jats:italic>Cryba1<\/jats:italic>\n                    loss disrupts its protein maturation, causing immature RET protein accumulation. This triggers age\u2010dependent endoplasmic reticulum (ER) stress, potentially contributing to the pathogenesis of AMD. Interestingly, although\n                    <jats:italic>Cryba1<\/jats:italic>\n                    is not identified as an AMD\u2010linked variant in current GWAS, its loss may be linked to AMD mechanisms. These findings underscore the potential of gene\u2010agnostic and epigenetic therapeutic strategies for treating AMD.\n                  <\/jats:p>","DOI":"10.1111\/acel.70163","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T12:29:40Z","timestamp":1752582580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Age\u2010Dependent Histone Deacetylase 3 Regulation by\n                    <scp>\u03b2A3<\/scp>\n                    \/\n                    <scp>A1<\/scp>\n                    \u2010Crystallin and Inositol Hexaphosphate in Retinal Pigmented Epithelial Cells Reveals a Novel Pathway in Age\u2010Related Macular Degeneration"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2281-9066","authenticated-orcid":false,"given":"Sujan","family":"Chatterjee","sequence":"first","affiliation":[{"name":"Nevada Institute of Personalized Medicine University of Nevada  Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayan","family":"Ghosh","sequence":"additional","affiliation":[{"name":"The Wilmer Eye Institute The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7734-5192","authenticated-orcid":false,"given":"Zachary","family":"Sin","sequence":"additional","affiliation":[{"name":"Nevada Institute of Personalized Medicine University of Nevada  Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8104-8652","authenticated-orcid":false,"given":"Vishnu Suresh","family":"Babu","sequence":"additional","affiliation":[{"name":"The Wilmer Eye Institute The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta Viera","family":"Preval","sequence":"additional","affiliation":[{"name":"Nevada Institute of Personalized Medicine University of Nevada  Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen","family":"Tran","sequence":"additional","affiliation":[{"name":"Nevada Institute of Personalized Medicine University of Nevada  Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Bammidi","sequence":"additional","affiliation":[{"name":"The Wilmer Eye Institute The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1194-3050","authenticated-orcid":false,"given":"Pooja","family":"Gautam","sequence":"additional","affiliation":[{"name":"The Wilmer Eye Institute The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Hose","sequence":"additional","affiliation":[{"name":"The Wilmer Eye Institute The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7204-6572","authenticated-orcid":false,"given":"Yuri","family":"Sergeev","sequence":"additional","affiliation":[{"name":"National eye Institute National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3421-3699","authenticated-orcid":false,"given":"Miguel","family":"Flores\u2010Bellver","sequence":"additional","affiliation":[{"name":"CellSight \u2010 Ocular Stem Cell and Regeneration Program, Department of Ophthalmology University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-1855","authenticated-orcid":false,"given":"Kevin","family":"Ritter","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Pharmacy, Institute of Organic Chemistry University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1025-9484","authenticated-orcid":false,"given":"Henning J.","family":"Jessen","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Pharmacy, Institute of Organic Chemistry University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0813-2943","authenticated-orcid":false,"given":"Issam","family":"Al Diri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1739-5577","authenticated-orcid":false,"given":"Debasish","family":"Sinha","sequence":"additional","affiliation":[{"name":"The Wilmer Eye Institute The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-7361","authenticated-orcid":false,"given":"Prasun","family":"Guha","sequence":"additional","affiliation":[{"name":"Nevada Institute of Personalized Medicine University of Nevada  Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.59"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201045839\u2010z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1139\/o01-032"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2023.09.006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","unstructured":"Chatterjee S. L. V.Preval Z.Sin et\u00a0al.2024.\u201cInositol Hexaphosphate (InsP6) Activates the HDAC1\/3 Epigenetic Axis to Maintain Intestinal Barrier Function.\u201dbioRxiv.https:\/\/doi.org\/10.1101\/2024.09.15.613154.","DOI":"10.1101\/2024.09.15.613154"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001570\u2010w"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500452k"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2013.10.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2007.123125"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003956\u20106"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0588-y"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18\u201024132"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912979107"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.02.013"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113070"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011262\u20101"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010023\u201001399\u2010w"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2023.08.023"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/589589"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2069437"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821552116"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1304670110"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.06.002"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.856853"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1630"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2013.02.005"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17\u201022161"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201503094"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12010146"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw257"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.40463"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197\u20100186(95)00001\u2010o"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.181"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010021\u201002386\u20106"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X18666200128125641"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1123621"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.27292"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125631"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201003856\u2010y"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11262"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10728"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.07.012"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302906110"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1286005"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.11.002"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70163","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70163","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70163","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:37:20Z","timestamp":1781854640000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,15]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/acel.70163"],"URL":"https:\/\/doi.org\/10.1111\/acel.70163","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,15]]},"assertion":[{"value":"2025-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70163"}}