{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:36:03Z","timestamp":1790048163880,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Somatic mitochondrial DNA (mtDNA) mutation accumulation has been observed in individuals with retinal degenerative disorders. To study the effects of aging and mtDNA mutation accumulation in the retina, a polymerase gamma (POLG) exonuclease\u2010deficient model, the Polg\n                    <jats:sup>D257A<\/jats:sup>\n                    mutator mice (D257A), was used. POLG is an enzyme responsible for regulating mtDNA replication and repair. Retinas of young and older mice with this mutation were analyzed in\u00a0vivo and ex\u00a0vivo to provide new insights into the contribution of age\u2010related mitochondrial (mt) dysfunction due to mtDNA damage. Optical coherence tomography (OCT) image analysis revealed a decrease in retinal and photoreceptor thickness starting at 6\u2009months of age in mice with the D257A mutation compared to wild\u2010type (WT) mice. Electroretinography (ERG) testing showed a significant decrease in all recorded responses at 6\u2009months of age. Sections labeled with markers of different types of retinal cells, including cones, rods, and bipolar cells, exhibited decreased labeling starting at 6\u2009months. However, electron microscopy analysis revealed differences in retinal pigment epithelium (RPE) mt morphology beginning at 3\u2009months. Interestingly, there was no increase in oxidative stress and parkin\u2010mediated mitophagy in the ages analyzed in the retina or RPE of D257A mice. Additionally, D257A RPE exhibited an accelerated rate of autofluorescence cytoplasmic granule formation and accumulation. Mt markers displayed different abundance in protein lysates obtained from retina and RPE samples. These findings suggest that the accumulation of mtDNA mutations leads to impaired mt function and accelerated aging, resulting in retinal degeneration.\n                  <\/jats:p>","DOI":"10.1111\/acel.14282","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T01:40:10Z","timestamp":1724982010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Modeling aging and retinal degeneration with mitochondrial\n                    <scp>DNA<\/scp>\n                    mutation burden"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0454-8201","authenticated-orcid":false,"given":"John","family":"Sturgis","sequence":"first","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute Cleveland Clinic  Cleveland Ohio USA"},{"name":"Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, School of Medicine Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupesh","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinn R.","family":"Caron","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivy S.","family":"Samuels","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute Cleveland Clinic  Cleveland Ohio USA"},{"name":"Research Service Louis Stokes Cleveland VA Medical Center  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Micheal","family":"Shiju","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Mukkara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute Cleveland Clinic  Cleveland Ohio USA"},{"name":"College of Arts and Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6166-5124","authenticated-orcid":false,"given":"Vera L.","family":"Bonilha","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute Cleveland Clinic  Cleveland Ohio USA"},{"name":"Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine, School of Medicine Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2023.04.003"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.07.014"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldt017"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2014.10.004"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2013.03.006"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495\u2010024\u201001977\u2010y"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2109286"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604572113"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology8020031"},{"issue":"7","key":"e_1_2_11_11_1","first-page":"583","article-title":"Lipofuscin and melanin of human retinal pigment epithelium. 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