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However, its role in corneal neovascularization (CoNV) remains unclear. <jats:italic>Methods. In vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models were assessed in hypoxia-stimulated angiogenesis and in a mouse model of alkali burn-induced 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. <jats:italic>Results.<\/jats:italic> In this study, we found that G9a was positively related to corneal alkali burn-induced injury. Inhibition of G9a with BIX 01294 (BIX) alleviated corneal injury, including oxidative stress and neovascularization <jats:italic>in vivo<\/jats:italic>. Similarly, inhibition of G9a with either BIX or small interfering RNA (siRNA) exerted an inhibitory effect on hypoxia\/reoxygenation (H\/R)-induced oxidative stress and angiogenesis in HUVECs. Moreover, our study revealed that ablation of reactive oxygen species (ROS) with N-acetyl-cysteine suppressed angiogenesis in HUVECs exposed to H\/R stimulation. Furthermore, NADPH oxidase 4 (Nox4), which was positively associated with ROS production and angiogenesis, was elevated during H\/R. This effect could be reversed through suppression of the transcription activity of G9a with BIX or siRNA. In addition, the Nrf2\/HO-1 pathway, upstream of Nox4, was activated in both BIX-treated mice and G9a-inhibited HUVECs. Collectively, our results demonstrated that inhibition of G9a-alleviated corneal angiogenesis by inhibiting Nox4-dependent ROS production through the Nrf2\/HO-1 signaling pathway. These findings indicate that G9a may be a valuable therapeutic target for CoNV.<\/jats:p>","DOI":"10.1155\/2020\/6983268","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T23:31:20Z","timestamp":1584142280000},"page":"1-14","source":"Crossref","is-referenced-by-count":6,"title":["G9a Suppression Alleviates Corneal Neovascularization through Blocking Nox4-Mediated Oxidative Stress"],"prefix":"10.1155","volume":"2020","author":[{"given":"Shanshan","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanju","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiao","family":"Pan","sequence":"additional","affiliation":[{"name":"Department 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