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Dry AMD is characterized by a progressive macular degeneration of the retinal pigment epithelium (RPE) and photoreceptors, and the RPE oxidative damage\/dystrophy is at the core of the disease. Recent population\/patients-based studies have shown an association of high free serum thyroid hormone (TH) levels with increased risk of AMD. This work investigated the effects of TH signaling inhibition on RPE and photoreceptor damage\/cell death in an oxidative stress-induced mouse model of AMD. TH signaling inhibition was achieved by anti-thyroid drug treatment and oxidative stress was induced by sodium iodate (NaIO<jats:sub>3<\/jats:sub>) administration. Mice treated with NaIO<jats:sub>3<\/jats:sub> showed severe RPE and photoreceptor cell death\/necroptosis, destruction, oxidative damage, retinal stress, and reduced retinal function. Treatment with anti-thyroid drug protected RPE and photoreceptors from damage\/cell death induced by NaIO<jats:sub>3<\/jats:sub>, reduced oxidative damage of RPE and photoreceptors, and preserved retinal function. Gene expression analysis showed that the NaIO<jats:sub>3<\/jats:sub>-induced RPE\/photoreceptor damage\/cell death involves multiple mechanisms, including cellular oxidative stress responses, activation of necroptosis\/apoptosis signaling, and inflammatory responses. Treatment with anti-thyroid drug abolished these cellular stress\/death responses. The findings of this study demonstrate a role of TH signaling in RPE and photoreceptor cell death after oxidative stress challenge, and support a role of TH signaling in the pathogenesis of AMD.<\/jats:p>","DOI":"10.1038\/s41419-019-2216-7","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T14:02:52Z","timestamp":1578924172000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Inhibition of thyroid hormone signaling protects retinal pigment epithelium and photoreceptors from cell death in a mouse model of age-related macular degeneration"],"prefix":"10.1038","volume":"11","author":[{"given":"Hongwei","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Qin","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"2216_CR1","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1001\/archopht.122.7.1019","volume":"122","author":"DS Friedman","year":"2004","unstructured":"Friedman, D. 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