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Here, we examine the therapeutic potential of ZLN005, a selective PGC\u20101<jats:italic>\u03b1<\/jats:italic> transcriptional regulator, in protecting RPE from cytotoxic oxidative damage. Gene expression analysis on ARPE\u201019 cells treated with ZLN005 shows robust upregulation of PGC\u20101<jats:italic>\u03b1<\/jats:italic> and its associated transcription factors, antioxidant enzymes, and mitochondrial genes. Energetic profiling shows that ZLN005 treatment enhances RPE mitochondrial function by increasing basal and maximal respiration rates, and spare respiratory capacity. In addition, ZLN005 robustly protects ARPE\u201019 cells from cell death caused by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, ox\u2010LDL, and NaIO<jats:sub>3<\/jats:sub> without exhibiting any cytotoxicity under basal conditions. ZLN005 protection against H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010mediated cell death was lost in PGC\u20101<jats:italic>\u03b1<\/jats:italic>\u2010silenced cells. Our data indicates that ZLN005 efficiently protects RPE cells from oxidative damage through selective induction of PGC\u20101<jats:italic>\u03b1<\/jats:italic> and its target antioxidant enzymes. ZLN005 may serve as a novel therapeutic agent for retinal diseases associated with RPE dystrophies.<\/jats:p>","DOI":"10.1155\/2018\/9248640","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T23:32:11Z","timestamp":1541460731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Pharmaceutical Induction of PGC\u20101<i>\u03b1<\/i> Promotes Retinal Pigment Epithelial Cell Metabolism and Protects against Oxidative Damage"],"prefix":"10.1155","volume":"2018","author":[{"given":"Sangeeta","family":"Satish","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Philipose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Aparecida 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