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EUK\u2010134 is a mimetic of SOD2 and catalase, widely used for its antioxidant properties in models of light\u2010induced damage or oxidative stress. However, its effects on the retina are not yet clear. Here, we investigated the capability of EUK\u2010134 in averting AMD using sodium iodate (NaIO<jats:sub>3<\/jats:sub>)\u2010induced Balb\/c mouse and ARPE\u201019 cells (adult RPE cell line). In vivo, EUK\u2010134 effectively antagonized NaIO<jats:sub>3<\/jats:sub>\u2010induced retinal deformation and prevented outer and inner nuclear layer thinning. In addition, it was found that the EUK\u2010134\u2010treated group significantly down\u2010regulated the expression of cleaved caspase\u20103 compared with the group treated with NaIO<jats:sub>3<\/jats:sub> alone. Our results found that EUK\u2010134 notably improved cell viability by preventing mitochondrial ROS accumulation\u2010induced membrane potential depolarization\u2010mediated apoptosis in NaIO<jats:sub>3<\/jats:sub>\u2010inducted ARPE\u201019 cells. Furthermore, we found that EUK\u2010134 could inhibit p\u2010ERK, p\u2010p38, p\u2010JNK, p\u2010p53, Bax, cleaved caspase\u20109, cleaved caspase\u20103, and cleaved PARP by increasing Bcl\u20102 protein expression. Additionally, we employed MAPK pathway inhibitors by SB203580 (a p38 inhibitor), U0126 (an ERK inhibitor), and SP600125 (a JNK inhibitor) to corroborate the aforementioned observation. The results support that EUK\u2010134 may effectively prevent mitochondrial oxidative stress\u2010mediated retinal apoptosis in NaIO<jats:sub>3<\/jats:sub>\u2010induced retinopathy.<\/jats:p>","DOI":"10.1002\/tox.24416","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T13:39:37Z","timestamp":1726234777000},"page":"88-100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Novel Application of <scp>EUK<\/scp>\u2010134 in Retinal Degeneration: Preventing Mitochondrial Oxidative Stress\u2010Triggered Retinal Pigment Epithelial Cell Apoptosis by Suppressing <scp>MAPK<\/scp>\/p53 Signaling Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Shang\u2010Chun","family":"Tsou","sequence":"first","affiliation":[{"name":"Department of Nutrition Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Ju","family":"Chuang","sequence":"additional","affiliation":[{"name":"Emergency Department St. Martin De Porres Hospital  Chiayi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin\u2010Lin","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Nutrition Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu\u2010Chun","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medicine Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui\u2010Hsuan","family":"Yeh","sequence":"additional","affiliation":[{"name":"Institute of Medicine Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology School of Medicine, Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Wang","sequence":"additional","affiliation":[{"name":"Rehabilitation Sciences &amp; Technology University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6395-4280","authenticated-orcid":false,"given":"Yuan\u2010Yen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology School of Medicine, Chung Shan Medical University  Taichung Taiwan"},{"name":"Clinical Laboratory Chung Shan Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Medicine Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Optometry Asia University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-66014-7_1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31550-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade9459"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5814"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154181"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12061183"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2022.926627"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-21255"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1029473"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10495"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2023.112654"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-008-0285-7"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00389"},{"key":"e_1_2_10_15_1","first-page":"441","article-title":"Bax Induces Cytochrome C Release by Multiple Mechanisms in Mitochondria From MCF7 Cells","volume":"45","author":"G\u00f3mez\u2010Cris\u00f3stomo N. 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