{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:25:01Z","timestamp":1789575901188,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2013,12]]},"abstract":"Summary<\/jats:title>\n \n The corneal endothelium (\n CE<\/jats:styled-content>\n ) is a single layer of cells lining the posterior face of the cornea providing metabolic functions essential for maintenance of corneal transparency. Adult\n CE<\/jats:styled-content>\n cells lack regenerative potential, and the number of\n CE<\/jats:styled-content>\n cells decreases throughout life. To determine whether endogenous\n DNA<\/jats:styled-content>\n damage contributes to the age\u2010related spontaneous loss of\n CE<\/jats:styled-content>\n , we characterized\n CE<\/jats:styled-content>\n in\n \n E<\/jats:styled-content>\n rcc1\n <\/jats:italic>\n \u2212\/\u0394<\/jats:sup>\n mice, which have impaired capacity to repair\n DNA<\/jats:styled-content>\n damage and age prematurely. Eyes from 4.5\u2010 to 6\u2010month\u2010old\n \n E<\/jats:styled-content>\n rcc1\n <\/jats:italic>\n \u2212\/\u0394<\/jats:sup>\n mice, age\u2010matched wild\u2010type (\n WT<\/jats:styled-content>\n ) littermates, and old\n WT<\/jats:styled-content>\n mice (24\u2010 to 34\u2010month\u2010old) were compared by spectral domain optical coherence tomography and corneal confocal microscopy. Histopathological changes in\n CE<\/jats:styled-content>\n were further identified in paraffin tissue sections, whole\u2010mount immunostaining, and scanning electron and transmission electron microscopy. The\n CE<\/jats:styled-content>\n of old\n WT<\/jats:styled-content>\n mice displayed polymorphism and polymegathism, polyploidy, decreased cell density, increased cell size, increases in\n D<\/jats:styled-content>\n escemet's thickness, and the presence of posterior projections originating from the\n CE<\/jats:styled-content>\n toward the anterior chamber, similar to changes documented for aging human corneas. Similar changes were observed in young adult\n \n E<\/jats:styled-content>\n rcc1\n <\/jats:italic>\n \u2212\/\u0394<\/jats:sup>\n mice\n CE<\/jats:styled-content>\n , demonstrating spontaneous premature aging of the\n CE<\/jats:styled-content>\n of these\n DNA<\/jats:styled-content>\n repair\u2013deficient mice.\n CD<\/jats:styled-content>\n 45\n +<\/jats:sup>\n immune cells were associated with the posterior surface of\n CE<\/jats:styled-content>\n from\n \n E<\/jats:styled-content>\n rcc1\n <\/jats:italic>\n \u2212\/\u0394<\/jats:sup>\n mice and the tissue expressed increased\n IL<\/jats:styled-content>\n \u20101\u03b1,\n C<\/jats:styled-content>\n xcl2, and\n TNF<\/jats:styled-content>\n \u03b1, pro\u2010inflammatory proteins associated with senescence\u2010associated secretory phenotype. These data provide strong experimental evidence that\n DNA<\/jats:styled-content>\n damage can promote aging of the\n CE<\/jats:styled-content>\n and that\n \n E<\/jats:styled-content>\n rcc1\n <\/jats:italic>\n \u2212\/\u0394<\/jats:sup>\n mice offer a rapid and accurate model to study\n CE<\/jats:styled-content>\n pathogenesis and therapy.\n <\/jats:p>","DOI":"10.1111\/acel.12143","type":"journal-article","created":{"date-parts":[[2013,8,8]],"date-time":"2013-08-08T11:21:44Z","timestamp":1375960904000},"page":"1122-1131","source":"Crossref","is-referenced-by-count":19,"title":["Age\u2010related dystrophic changes in corneal endothelium from\n DNA<\/scp>\n repair\u2013deficient mice"],"prefix":"10.1111","volume":"12","author":[{"given":"Danny S.","family":"Roh","sequence":"first","affiliation":[{"name":"Department of Ophthalmology University of Pittsburgh School of Medicine 203 Lothrop St. Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Pittsburgh School of Medicine 203 Lothrop St. Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Gabriele","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Pittsburgh School of Medicine 203 Lothrop St. Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andria R.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Pittsburgh School of Public Health 130 DeSoto Street Pittsburgh PA 15261 USA"},{"name":"University of Pittsburgh Cancer Institute Hillman Cancer Center 5117 Centre Ave, 2.6 Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Niedernhofer","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Cancer Institute Hillman Cancer Center 5117 Centre Ave, 2.6 Pittsburgh PA 15213 USA"},{"name":"Department of Microbiology and Molecular Genetics University of Pittsburgh School of Medicine 523 Bridgeside Point II 450 Technology Drive Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Funderburgh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Pittsburgh School of Medicine 203 Lothrop St. Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,1]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00293-08"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1475-1313.1999.00408.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2003.08.002"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2233"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1851"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2005.11.008"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.91"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1581"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5662"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-007-9177-z"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2011.04.010"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2011.04.026"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm1065"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-9071.2009.02016.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.10.002"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.06.021"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(86)80093-8"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1982.01030040922011"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(02)00065-4"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.06.012"},{"key":"e_1_2_6_22_1","first-page":"897","article-title":"Decreasing expression of the G1\u2010phase inhibitors, p21Cip1 and p16INK4a, promotes division of corneal endothelial cells from older donors","volume":"16","author":"Joyce NC","year":"2010","journal-title":"Mol. 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