biostudies-literatureTang XNational Eye InstituteNEI NIH HHSResearch to Prevent BlindnessBrightFocus Foundation363-377https://www.ebi.ac.uk/biostudies/studies/S-EPMC8126573biostudies-literatureUnknown24(2)NADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidases playing an important role in many biological processes. Previously we have shown that Nox4 is highly expressed in retinal blood vessels and is upregulated in oxygen-induced retinopathy (OIR). However, the exact role of endothelial Nox4 in retinal angiogenesis remains elusive. Herein, using endothelial cell (EC)-specific Nox4 knockout (Nox4^EC-KO) mice, we investigated the impact of endothelial Nox4 deletion on retinal vascular development and pathological angiogenesis during OIR. Our results show that deletion of Nox4 in ECs led to retarded retinal vasculature development with fewer, blunted-end tip cells and sparser, dysmorphic filopodia at vascular front, and reduced density of vascular network in superficial, deep, anAngiogenesisEndothelium-specific deletion of Nox4 delays retinal vascular development and mitigates pathological angiogenesis.PMC8126573EY030970EY025061R01 EY019949an Unrestricted Grant to the Department of Ophthalmology, the State University of New York at BuffaloR21 EY025061R01 EY030970EY019949NGR G2019302Chen YWang JJZhang SXWang JAbboud HETang XfalseEndothelium-specific deletion of Nox4 delays retinal vascular development and mitigates pathological angiogenesis.NADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidases playing an important role in many biological processes. Previously we have shown that Nox4 is highly expressed in retinal blood vessels and is upregulated in oxygen-induced retinopathy (OIR). However, the exact role of endothelial Nox4 in retinal angiogenesis remains elusive. Herein, using endothelial cell (EC)-specific Nox4 knockout (Nox4^EC-KO) mice, we investigated the impact of endothelial Nox4 deletion on retinal vascular development and pathological angiogenesis during OIR. Our results show that deletion of Nox4 in ECs led to retarded retinal vasculature development with fewer, blunted-end tip cells and sparser, dysmorphic filopodia at vascular front, and reduced density of vascular network in superficial, deep, an2021-01-01T00:00:00Z2021 May2025-04-04T10:17:27.27Z2025-04-04T10:17:27.27ZS-EPMC81265733320137210.1007/s10456-020-09757-3