{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T01:14:00Z","timestamp":1780881240224,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004092","name":"Kuopion Yliopistollinen Sairaala","doi-asserted-by":"publisher","award":["5503743"],"award-info":[{"award-number":["5503743"]}],"id":[{"id":"10.13039\/501100004092","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Research Council of the Academy of Finland","award":["296840 and 333302"],"award-info":[{"award-number":["296840 and 333302"]}]},{"name":"National Science Centre Poland","award":["2017\/27\/B\/NZ3\/00872"],"award-info":[{"award-number":["2017\/27\/B\/NZ3\/00872"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. In our previous studies, we found that deficiencies in the nuclear factor, erythroid 2 like 2 (NFE2L2) and peroxisome proliferator-activated receptor gamma coactivator 1-\u03b1 (PGC-1\u03b1) genes caused AMD-like pathological phenotypes in mice. In the present work, we show hijacked epithelial-mesenchymal transition (EMT) due to the common loss of PGC-1\u03b1 and NFE2L2 (double knock-out, dKO) genes in aged animals. The implanted area was assessed by histology, immunohistochemistry and transmission electron microscopy. Confocal microscopy revealed altered regions in the filamentous actin ring. This contrasted with hexagonal RPE morphology in wild-type mice. The ultrastructural RPE features here illustrated loss of apical microvilli, alteration of cell-cell contact, loss of basal in-folding with deposits on Bruch\u2019s membrane, and excessive lipofuscin deposition in dKO samples. We also found the expression of epithelial-mesenchymal transition transcription factors, such as Snail, Slug, collagen 1, vimentin and OB-cadherin, to be significantly different in dKO RPEs. An increased immunoreactivity of senescence markers p16, DEC1 and HMGB1 was also noted. These findings suggest that EMT and senescence pathways may intersect in the retinas of dKO mice. Both processes can be activated by damage to the RPE, which may be caused by increased oxidative stress resulting from the absence of NFE2L2 and PGC-1\u03b1 genes, important for antioxidant defense. This dKO model may provide useful tools for studying AMD pathogenesis and evaluating novel therapies for this disease.<\/jats:p>","DOI":"10.3390\/ijms22041684","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T23:43:16Z","timestamp":1612914196000},"page":"1684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Epithelial-Mesenchymal Transition and Senescence in the Retinal Pigment Epithelium of NFE2L2\/PGC-1\u03b1 Double Knock-Out Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9539-9584","authenticated-orcid":false,"given":"Janusz","family":"Blasiak","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141\/143, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Koskela","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-4783","authenticated-orcid":false,"given":"Elzbieta","family":"Pawlowska","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Medical University of Lodz, 92-217 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4259-4041","authenticated-orcid":false,"given":"Mikko","family":"Liukkonen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Ruuth","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Toropainen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha M. T.","family":"Hyttinen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Viiri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Turku Bioscience Centre, University of Turku and \u00c5bo Akademi University, 20520 Turku, Finland"},{"name":"Cell Biology, Faculty of Science and Technology, \u00c5bo Akademi University, 20500 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-931X","authenticated-orcid":false,"given":"Heping","family":"Xu","sequence":"additional","affiliation":[{"name":"The Wellcome-Wolfson Institute of Experimental Medicine Queen\u2019s University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[{"name":"The Wellcome-Wolfson Institute of Experimental Medicine Queen\u2019s University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs","family":"Felszeghy","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Eastern Finland, Yliopistonranta 1 A, 70211 Kuopio, Finland"},{"name":"Institute of Dentistry, University of Eastern Finland, Yliopistonranta 1 C, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaarniranta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland"},{"name":"Department of Ophthalmology, Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1172\/JCI200320530","article-title":"Epithelial-mesenchymal transition and its implications for fibrosis","volume":"112","author":"Kalluri","year":"2003","journal-title":"J. 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