{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:46:56Z","timestamp":1793148416094,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8K1341"],"award-info":[{"award-number":["CMRPG8K1341"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["110-2314-B-182A-117"],"award-info":[{"award-number":["110-2314-B-182A-117"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    Excessive reactive oxygen species (ROS) contribute to damage of retinal cells and the development of retinal diseases including age\u2010related macular degeneration (AMD). ROS result in increased metabolites of lipoxygenases (LOXs), which react with ROS to induce lipid peroxidation and may lead to ferroptosis. In this study, the effect of 5\u2010LOX inhibition on alleviating ROS\u2010induced cell death was evaluated using sodium iodate (NaIO\n                    <jats:sub>3<\/jats:sub>\n                    ) in the retinal pigment epithelium (RPE) cell line ARPE\u201019 and a mouse model investigating oxidative stress in AMD. We demonstrated that NaIO\n                    <jats:sub>3<\/jats:sub>\n                    induced cell death in the RPE cells through mechanisms including ferroptosis. Inhibition of 5\u2010LOX with specific inhibitor, Zileuton, or siRNA knockdown of\n                    <jats:italic>ALXO5<\/jats:italic>\n                    mitigated NaIO\n                    <jats:sub>3<\/jats:sub>\n                    \u2010induced lipid peroxidation, mitochondrial damage, DNA impairment, and cell death in ARPE\u201019 cells. Additionally, in the mouse model, pretreatment with Zileuton reduced the NaIO\n                    <jats:sub>3<\/jats:sub>\n                    \u2010induced lipid peroxidation of RPE cells, cell death in the photoreceptor layer of the retina, inflammatory responses, and degeneration of both the neuroretina and RPE monolayer cells. Our results suggest that 5\u2010LOX plays a crucial role in ROS\u2010induced cell death in the RPE and that regulating 5\u2010LOX activity could be a useful approach to control ROS and ferroptosis\u2010induced damage, which promote degeneration in retinal diseases.\n                  <\/jats:p>","DOI":"10.1155\/2022\/1792894","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T20:35:09Z","timestamp":1645648509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["5\u2010Lipoxygenase Inhibition Protects Retinal Pigment Epithelium from Sodium Iodate\u2010Induced Ferroptosis and Prevents Retinal 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