{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:33:36Z","timestamp":1787891616180,"version":"build-2784847793"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T00:00:00Z","timestamp":1411603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY019037-S"],"award-info":[{"award-number":["EY019037-S"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Although chronic inflammation is believed to contribute to the pathology of age\u2010related macular degeneration (<jats:styled-content style=\"fixed-case\">AMD<\/jats:styled-content>), knowledge regarding the events that elicit the change from para\u2010inflammation to chronic inflammation in the pathogenesis of <jats:styled-content style=\"fixed-case\">AMD<\/jats:styled-content> is lacking. We propose here that lipocalin\u20102 (<jats:styled-content style=\"fixed-case\">LCN<\/jats:styled-content>2), a mammalian innate immunity protein that is trafficked to the lysosomes, may contribute to this process. It accumulates significantly with age in retinal pigment epithelial (<jats:styled-content style=\"fixed-case\">RPE<\/jats:styled-content>) cells of <jats:italic>Cryba1<\/jats:italic> conditional knockout (<jats:styled-content style=\"fixed-case\">cKO<\/jats:styled-content>) mice, but not in control mice. We have recently shown that these mice, which lack \u03b2A3\/A1\u2010crystallin specifically in <jats:styled-content style=\"fixed-case\">RPE<\/jats:styled-content>, have defective lysosomal clearance. The age\u2010related increase in <jats:styled-content style=\"fixed-case\">LCN<\/jats:styled-content>2 in the <jats:styled-content style=\"fixed-case\">cKO<\/jats:styled-content> mice is accompanied by increases in chemokine (<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> motif) ligand 2 (<jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>2), reactive gliosis, and immune cell infiltration. <jats:styled-content style=\"fixed-case\">LCN<\/jats:styled-content>2 may contribute to induction of a chronic inflammatory response in this mouse model with <jats:styled-content style=\"fixed-case\">AMD<\/jats:styled-content>\u2010like pathology.<\/jats:p>","DOI":"10.1111\/acel.12274","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T12:12:05Z","timestamp":1411647125000},"page":"1091-1094","source":"Crossref","is-referenced-by-count":33,"title":["Increased <scp>L<\/scp>ipocalin\u20102 in the retinal pigment epithelium of <i>Cryba1<\/i> c<scp>KO<\/scp> mice is associated with a chronic inflammatory response"],"prefix":"10.1111","volume":"13","author":[{"given":"Mallika","family":"Valapala","sequence":"first","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malia","family":"Edwards","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Hose","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda","family":"Grebe","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran A.","family":"Bhutto","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Cano","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Berger","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research and Ontario Cancer Institute University Health Network Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak W.","family":"Mak","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research and Ontario Cancer Institute University Health Network Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wawrousek","sequence":"additional","affiliation":[{"name":"National Eye Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Handa","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard A.","family":"Lutty","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"J.","family":"Samuel Zigler","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debasish","family":"Sinha","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3459"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510847103"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222551899"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03104"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.08.084"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/650493"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2475"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.24546"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.125773"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.3231"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.05.008"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07201"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.06.003"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-87"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2007.08.016"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.097683"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.27292"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/348092"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.06.001"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.078790"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facel.12274","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.12274","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.12274","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.12274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T05:24:09Z","timestamp":1696397049000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.12274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,25]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["10.1111\/acel.12274"],"URL":"https:\/\/doi.org\/10.1111\/acel.12274","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,25]]}}}