ArticleJournal of diabetes research2015
NADPH oxidase 4-derived H2O2 promotes aberrant retinal neovascularization via activation of VEGF receptor 2 pathway in oxygen-induced retinopathy.
Article in Journal of diabetes research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 8 citations in OpenAlex.
- The role of immunoproteasome in diabetes and diabetes-related complications.Genes & diseases · 2026Review
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- Review: The role of microglia in diabetic retinopathy and its potential as a therapeutic target.Molecular vision · 2026Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Article
- Redox Regulation of Immunometabolism in Microglia Underpinning Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2024Review
- Unveiling the Role of Endothelial Dysfunction: A Possible Key to Enhancing Catheter Ablation Success in Atrial Fibrillation.International journal of molecular sciences · 2024Review
- Effects of Nox4 upregulation on PECAM-1 expression in a mouse model of diabetic retinopathy.PloS one · 2024Article
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Sustained Upregulation of Endothelial Nox4 Mediates Retinal Vascular Pathology in Type 1 Diabetes.Diabetes · 2023Article
- Identification of potential ferroptosis-related biomarkers and a pharmacological compound in diabetic retinopathy based on machine learning and molecular docking.Frontiers in endocrinology · 2022Article
- Apocynin ameliorates NADPH oxidase 4 (NOX4) induced oxidative damage in the hypoxic human retinal Müller cells and diabetic rat retina.Molecular and cellular biochemistry · 2021Article
- Endothelium-specific deletion of Nox4 delays retinal vascular development and mitigates pathological angiogenesis.Angiogenesis · 2021Article
- NADPH oxidase-induced oxidative stress in the eyes of hypertensive rats.Molecular vision · 2021Article
- Genetics of diabetes mellitus and diabetes complications.Nature reviews. Nephrology · 2020Review
- Observational
- Perturbed Biochemical Pathways and Associated Oxidative Stress Lead to Vascular Dysfunctions in Diabetic Retinopathy.Oxidative medicine and cellular longevity · 2019Review
- Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases.Oxidative medicine and cellular longevity · 2019Review
- A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes.Acta ophthalmologica · 2018Article
- The Role of Midkine in Arteriogenesis, Involving Mechanosensing, Endothelial Cell Proliferation, and Vasodilation.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
NADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidase in retinal endothelial cells. Our previous study suggests that upregulation of Nox4 in retinal endothelial cells contributes to retinal vascular leakage in diabetes. In the current study, we investigated the role and mechanism of Nox4 in regulation of retinal neovascularization (NV), a hallmark of proliferative diabetic retinopathy (PDR), using a mouse model of oxygen-induced retinopathy (OIR). Our results confirmed that Nox4 was expressed predominantly in retinal vasculature of mouse retina. Retinal expression of Nox4 was markedly increased in OIR, in parallel with enhanced phosphorylation of ERK. In human retinal microvascular endothelial cells (HRECs), overexpression of Nox4 by adenovirus significantly increased extracellular H2O2 generation, resulting in intensified VEGFR2 activation and exacerbated angiogenesis upon VEGF stimulation. In contrast, silencing Nox4 expression or scavenging H2O2 by polyethylene glycol- (PEG-) conjugated catalase inhibited endothelial migration, tube formation, and VEGF-induced activation of VEGFR2 signaling. Importantly, knockdown of retinal Nox4 by adenovirus-delivered siRNA significantly reduced ERK activation and attenuated retinal NV formation in OIR. Taken together, our data indicate that Nox4 promotes retinal NV formation through H2O2/VEGFR2/ERK signaling pathway. Reducing retinal Nox4 expression may represent a promising therapeutic approach for neovascular retinal diseases such as PDR.
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Registered trials
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