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However, its role in corneal neovascularization (CoNV) remains unclear. In vitro and in vivo models were assessed in hypoxia\u2010stimulated angiogenesis and in a mouse model of alkali burn\u2010induced CoNV. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions and different reoxygenation times to identify the molecular mechanisms involved in this process. In this study, we found that EZH2 was positively related to corneal alkali burn\u2010induced injury. Inhibition of EZH2 with 3\u2010Deazaneplanocin A (DZNeP) alleviated corneal injury, including oxidative stress and neovascularization in vivo. Similarly, inhibition of EZH2 with either DZNeP or small interfering RNA (siRNA) exerted an inhibitory effect on hypoxia\/reoxygenation (H\/R)\u2010induced oxidative stress and angiogenesis in HUVECs. Moreover, our study revealed that ablation of reactive oxygen species (ROS) with N\u2010acetyl\u2010cysteine suppressed angiogenesis in HUVECs exposed to H\/R stimulation. Furthermore, Forkhead\u2010box protein O3a (FoxO3a), which was positively associated with ROS production and angiogenesis, was elevated during H\/R. This effect could be reversed through the suppression of the transcription activity of EZH2 with DZNeP or siRNA. In addition, the PI3K\/Akt pathway, which is the upstream of FoxO3a, was activated in both DZNeP\u2010treated mice and EZH2\u2010inhibited HUVECs. Collectively, our results demonstrated that the inhibition of EZH2 alleviated corneal angiogenesis by inhibiting FoxO3a\u2010dependent ROS production through the PI3K\/Akt signaling pathway. These findings indicate that EZH2 may be a valuable therapeutic target for CoNV.<\/jats:p>","DOI":"10.1096\/fj.201902814rrr","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T14:23:52Z","timestamp":1596032632000},"page":"10168-10181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Inhibition of EZH2 alleviates angiogenesis in a model of corneal neovascularization by blocking FoxO3a\u2010mediated oxidative stress"],"prefix":"10.1096","volume":"34","author":[{"given":"Shan\u2010Shan","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Miao","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Renmin Hospital of Wuhan University Wuhan 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