{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:08:34Z","timestamp":1787170114092,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W004682\/1"],"award-info":[{"award-number":["MR\/W004682\/1"]}],"id":[{"id":"10.13039\/501100000265","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 retinal degeneration, such as diabetic retinopathy and age\u2010related macular degeneration, are major causes of blindness in modern society. Recent studies suggest that dysbiosis and intraocular translocation of bacteria from the blood circulation are critically involved in retinal degeneration. We hypothesise that the blood\u2010retinal barrier (BRB) cells can protect the neuroretina from blood\u2010borne pathogens by producing antimicrobial peptides (AMPs). The antimicrobial activity may decline during ageing, putting the retina at risk of low\u2010degree chronic inflammation and degeneration. Here, we found that the retinal pigment epithelial (RPE) cells, which form the outer BRB, express a variety of AMPs\/AMP precursors, including\n                    <jats:italic>APP<\/jats:italic>\n                    ,\n                    <jats:italic>RARRES2<\/jats:italic>\n                    ,\n                    <jats:italic>FAM3A<\/jats:italic>\n                    ,\n                    <jats:italic>HAMP<\/jats:italic>\n                    ,\n                    <jats:italic>CAMP<\/jats:italic>\n                    ,\n                    <jats:italic>GNLY<\/jats:italic>\n                    , and\n                    <jats:italic>PI3<\/jats:italic>\n                    . Senescent RPE cells expressed lower levels of\n                    <jats:italic>APP<\/jats:italic>\n                    and\n                    <jats:italic>RARRES2<\/jats:italic>\n                    mRNA, accompanied by increased intracellular retention of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>E. coli<\/jats:italic>\n                    <\/jats:styled-content>\n                    in a bactericidal assay. Silencing\n                    <jats:italic>APP<\/jats:italic>\n                    , not\n                    <jats:italic>RARRES2<\/jats:italic>\n                    , with shRNA reduced the antibacterial activity of RPE cells. Senescent RPE cells had lower levels of \u03b1\u2010secretase and higher levels of \u03b2\u2010secretase (\n                    <jats:italic>BACE1<\/jats:italic>\n                    ) and \u03b3\u2010secretase (\n                    <jats:italic>PS1<\/jats:italic>\n                    ), accompanied by reduced soluble APP\u03b1 and increased amyloid beta (A\u03b2) production, particularly the A\u03b242 isoform. Eyes from aged donors showed a higher A\u03b2 accumulation within RPE cells. Our results suggest that while RPE cells possess antimicrobial activity, this ability declines with age and is impaired in senescent cells. The impaired antimicrobial activity and augmented A\u03b2 deposition in senescent RPE cells may contribute to age\u2010related retinal para\u2010inflammation and neurodegeneration.\n                  <\/jats:p>","DOI":"10.1111\/acel.70161","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T05:10:26Z","timestamp":1752469826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Senescence Alters Antimicrobial Peptide Expression and Induces Amyloid\u2010\u03b2 Production in Retinal Pigment Epithelial Cells"],"prefix":"10.1111","volume":"24","author":[{"given":"Jian","family":"Liu","sequence":"first","affiliation":[{"name":"Aier Academy of Ophthalmology Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caijiao","family":"Yi","sequence":"additional","affiliation":[{"name":"Aier Eye Institute Changsha Aier Eye Hospital  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Qi","sequence":"additional","affiliation":[{"name":"Aier Academy of Ophthalmology Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexue","family":"Cui","sequence":"additional","affiliation":[{"name":"Aier Academy of Ophthalmology Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangling","family":"Yuan","sequence":"additional","affiliation":[{"name":"Aier Academy of Ophthalmology Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Deng","sequence":"additional","affiliation":[{"name":"Aier Eye Institute Changsha Aier Eye Hospital  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[{"name":"The Wellcome\u2010Wolfson Institute for Experimental Medicine Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-931X","authenticated-orcid":false,"given":"Heping","family":"Xu","sequence":"additional","affiliation":[{"name":"Aier Academy of Ophthalmology Central South University  Changsha Hunan China"},{"name":"Aier Eye Institute Changsha Aier Eye Hospital  Changsha Hunan China"},{"name":"The Wellcome\u2010Wolfson Institute for Experimental Medicine Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058709"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30488-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.10.003"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1522"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddad007"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3465"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00245-6"},{"key":"e_1_2_11_9_1","first-page":"184","article-title":"Amyloid\u2010Beta Is Found in Drusen From Some Age\u2010Related Macular Degeneration Retinas, but Not in Drusen From Normal Retinas","volume":"9","author":"Dentchev T.","year":"2003","journal-title":"Molecular Vision"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2007.07.025"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-023-03111-z"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.10.2540"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.27"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-019-00732-3"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720510790274491"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2101"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.013"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505625200"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3622"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15120-3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.7.21"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2023.08.11"},{"key":"e_1_2_11_23_1","first-page":"24","article-title":"Immunoreactivity Against Tau, Amyloid Precursor Protein, and Beta\u2010Amyloid in the Human Retina","volume":"36","author":"L\u00f6ffler K. U.","year":"1995","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14554"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajoc.2023.101911"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc1450"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31550-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2017.00014"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2012.10.002"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2005.07.009"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.12.082"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9071464"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.01.040"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03397-2"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.01056"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2023.1198241"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwi130"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2018.03.001"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009505"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01159-5"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01506"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12942"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11030777"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M400333-JLR200"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108204"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.01.001"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.14032"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.06.001"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13050790"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24635"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70161","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70161","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:37:29Z","timestamp":1781854649000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,13]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/acel.70161"],"URL":"https:\/\/doi.org\/10.1111\/acel.70161","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,13]]},"assertion":[{"value":"2024-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70161"}}