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AMD is classified as early, intermediate, advanced non-neovascular, and advanced neovascular forms depending on the clinical features. However, the exact pathogenesis remains unclear. Retinal pigment epithelium (RPE) cells degeneration is a hallmark of AMD. With aging, lipofuscin accumulates in RPE cells. N-retinylidene-N-retinylethanolamine (named A2E), a well-known fluorophore of lipofuscin, may contribute to RPE cells degeneration. In this study, we showed that photosensitization of A2E increased DNA damage, including telomere deprotection and deletion, and triggered cellular senescence. In addition, we found that the antioxidant N-acetyl-cysteine (NAC) partially alleviated this DNA damage. Telomerase overexpression rescued A2E-mediated RPE cell senescence, indicating that telomere dysfunction plays an important role in A2E-based senescence. We further showed that the senescence induced by A2E photosensitization may affect the microenvironment of the retina by expressing several factors of the secretory phenotype (SASP) including IL1B, IL13RA2, and CXCR4 through the NF-\u03baB pathway. We propose that expression of these factors create a pro-inflammatory environment that drives retina degeneration. Moreover, our findings suggest that protecting telomeres is a valuable strategy for treating retinal degeneration diseases, such as AMD.<\/jats:p>","DOI":"10.1038\/s41419-017-0200-7","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T10:55:28Z","timestamp":1518000928000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Photosensitization of A2E triggers telomere dysfunction and accelerates retinal pigment epithelium senescence"],"prefix":"10.1038","volume":"9","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiji","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueting","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,7]]},"reference":[{"key":"200_CR1","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.ophtha.2004.10.047","volume":"112","author":"TE Clemons","year":"2005","unstructured":"Clemons, T. 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