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NADPH oxidase (Nox) proteins are professional ROS\u2010generating enzymes, and therapeutic targeting in these diseases has strong appeal. Pharmacological inhibition of Nox4 reduces the severity of experimental retinal vasculopathy. We investigated the potential application of this drug approach in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Differential Nox enzyme expression was studied by real\u2010time\u2010quantitative polymerase chain reaction in primary human retinal endothelial cell isolates and a characterized human retinal endothelial cell line. Oxidative stress was triggered chemically in endothelial cells, by treatment with dimethyloxalylglycine (DMOG; 100 \u03bcM); Nox4 and vascular endothelial growth factor (VEGFA) transcript were measured; and production of ROS was detected by 2\u2032,7\u2032\u2010dichlorofluorescein. DMOG\u2010stimulated endothelial cells were treated with two Nox1\/Nox4 inhibitors, GKT136901 and GKT137831; cell growth was monitored by DNA quantification, in addition to VEGFA transcript and ROS production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nox4 (isoform Nox4A) was the predominant Nox enzyme expressed by human retinal endothelial cells. Treatment with DMOG significantly increased endothelial cell expression of Nox4 over 72 h, accompanied by ROS production and increased VEGFA expression. Treatment with GKT136901 or GKT137831 significantly reduced DMOG\u2010induced ROS production and VEGFA expression by endothelial cells, and the inhibitory effect of DMOG on cell growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings in experiments on activated human retinal endothelial cells provide translational corroboration of studies in experimental models of retinal vasculopathy and support the therapeutic application of Nox4 inhibition by GKT136901 and GKT137831 in patients with retinal vascular diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.13155","type":"journal-article","created":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T14:16:49Z","timestamp":1516717009000},"page":"652-660","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Effect of NADPH oxidase 1 and 4 blockade in activated human retinal endothelial cells"],"prefix":"10.1111","volume":"46","author":[{"given":"Binoy","family":"Appukuttan","sequence":"first","affiliation":[{"name":"Eye and Vision Health, College of Medicine and Public Health Flinders University  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuefang","family":"Ma","sequence":"additional","affiliation":[{"name":"Eye and Vision Health, College of Medicine and Public Health Flinders University  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Stempel","sequence":"additional","affiliation":[{"name":"Eye and Vision Health, College of Medicine and Public Health Flinders University  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam M","family":"Ashander","sequence":"additional","affiliation":[{"name":"Eye and Vision Health, College of Medicine and Public Health Flinders University  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devy","family":"Deliyanti","sequence":"additional","affiliation":[{"name":"Diabetic Retinopathy, Department of Diabetes Monash University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L","family":"Wilkinson\u2010Berka","sequence":"additional","affiliation":[{"name":"Diabetic Retinopathy, Department of Diabetes Monash University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4756-5493","authenticated-orcid":false,"given":"Justine R","family":"Smith","sequence":"additional","affiliation":[{"name":"Eye and Vision Health, College of Medicine and Public Health Flinders University  Adelaide South Australia Australia"},{"name":"South Australian Health and Medical Research Institute  Adelaide South Australia 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