{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:29:31Z","timestamp":1776086971426,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":43,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104935"],"award-info":[{"award-number":["82104935"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20252BAC240450"],"award-info":[{"award-number":["20252BAC240450"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012249","name":"Jiangxi University of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["XJ-S202468"],"award-info":[{"award-number":["XJ-S202468"]}],"id":[{"id":"10.13039\/501100012249","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetics Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Age\u2010related macular degeneration (AMD), particularly its non\u2010neovascular (dry) form, is a progressive retinal disorder that causes central vision loss and substantial impairment in daily life. Inflammation and immune dysregulation are recognized as core drivers of AMD, yet the contribution of PANoptosis, a form of programmed cell death that integrates pyroptosis, apoptosis, and necroptosis, remains unclear. In this study, we integrated human single\u2010cell transcriptomic and bulk microarray datasets from the retina and retinal pigment epithelium\u2013choroid to characterize PANoptosis\u2010related transcriptional changes in dry AMD. Dimensionality reduction, cell\u2010type annotation, and PANoptosis gene\u2010set scoring revealed a distinct PANoptosis signature enriched in AMD, with particularly strong activation in myeloid populations. By combining differential expression analysis with machine learning\u2010based feature selection, we identified four PANoptosis\u2010related genes (PON2, BNIP3, EPHB6, and TPD52) that robustly distinguished AMD from control samples and were associated with an altered immune microenvironment. Genetic instrument analysis further suggested a positive association between TPD52 expression and AMD risk. At the cellular level, our data highlighted macrophages, especially pro\u2010inflammatory M1\u2010like macrophages, as key coordinators of PANoptosis\u2010related pathways in dry AMD. To validate these findings in vivo, we used a sodium iodate\u2010induced mouse model of dry AMD and observed significant dysregulation of PON2, BNIP3, EPHB6, and TPD52 in the retina by RT\u2010qPCR, consistent with the human transcriptomic results and supporting their involvement in retinal degeneration and inflammation. Together, these findings implicate PANoptosis as an important and previously underappreciated component of dry AMD pathophysiology, define a four\u2010gene PANoptosis\u2010related signature with diagnostic potential, and suggest new molecular targets for therapeutic intervention.<\/jats:p>","DOI":"10.1155\/genr\/8903808","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:17:51Z","timestamp":1771046271000},"source":"Crossref","is-referenced-by-count":1,"title":["PANoptosis\u2010Related Diagnostic Biomarkers in Non\u2010Neovascular Age\u2010Related Macular Degeneration: An Integrative Transcriptomic and Experimental Study"],"prefix":"10.1155","volume":"2026","author":[{"given":"Jiaming","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yirong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinshang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6635-5898","authenticated-orcid":false,"given":"Binglin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19052548"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pop.2015.05.009"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.12.016"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.09.011"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.453"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu223"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/opo.12675"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197279"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200508"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13279"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.895519"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012776"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4402"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1294459"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00406"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00889-0"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.025"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.11.002"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109660"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.136720"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e27302"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.346545"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-98174-X"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00973-6"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.49890"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-021-04258-3"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.03.009"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124271"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2016.09.002"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3430"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2016.05.009"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-024-00709-Z"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12101820"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.765"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2162245"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1899-0"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-09-2000"},{"key":"e_1_2_12_40_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2016.3690"},{"key":"e_1_2_12_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-4623-4"}],"container-title":["Genetics Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/genr\/8903808","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/genr\/8903808","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/genr\/8903808","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:53:11Z","timestamp":1773312791000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/genr\/8903808"}},"subtitle":[],"editor":[{"given":"Xiaoye","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/genr\/8903808"],"URL":"https:\/\/doi.org\/10.1155\/genr\/8903808","archive":["Portico"],"relation":{},"ISSN":["0016-6723","1469-5073"],"issn-type":[{"value":"0016-6723","type":"print"},{"value":"1469-5073","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"8903808"}}