ArticlePloS one2013
Diabetes-induced superoxide anion and breakdown of the blood-retinal barrier: role of the VEGF/uPAR pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 22 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study.American journal of ophthalmology · 2021Trial
- ASSOCIATION BETWEEN EARLY ANATOMIC RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND LONG-TERM OUTCOME IN DIABETIC MACULAR EDEMA: An Independent Analysis of Protocol i Study Data.Retina (Philadelphia, Pa.) · 2019Trial
- Inhibiting the uPAR/FPR1 interactions reduces blood-retinal barrier breakdown and improves retinal function in a rat model of diabetes.Frontiers in neuroscience · 2026Article
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- A new perspective on protecting the blood-retinal barrier against injury in diabetic retinopathy: mitophagy.Frontiers in endocrinology · 2025Review
- Macular vessel density in patients with refractory diabetic macular edema in different stages of nonproliferative diabetic retinopathy.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2025Article
- Exploring the angiographic-biologic phenotype in the IMAGINE study: quantitative UWFA and cytokine expression.The British journal of ophthalmology · 2022Article
- Time-Course Changes in Oxidative Stress and Inflammation in the Retinas of rds Mice: A Retinitis Pigmentosa Model.Antioxidants (Basel, Switzerland) · 2022Article
- GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target.Cells · 2022Review
- Wnt Signaling in Inner Blood-Retinal Barrier Maintenance.International journal of molecular sciences · 2021Review
- Emerging Roles of Dyslipidemia and Hyperglycemia in Diabetic Retinopathy: Molecular Mechanisms and Clinical Perspectives.Frontiers in endocrinology · 2021Review
- Changes in the Systemic Expression of Sirtuin-1 and Oxidative Stress after Intravitreal Anti-Vascular Endothelial Growth Factor in Patients with Retinal Vein Occlusion.Biomolecules · 2020Observational
- Review
- Protective effect of myricetin derivatives fromMolecular vision · 2019Article
- High Glucose-Mediated Tyrosine Nitration of PI3-Kinase: A Molecular Switch of Survival and Apoptosis in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2018Article
- Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System.Journal of diabetes research · 2017Article
- Correction: Diabetes-Induced Superoxide Anion and Breakdown of the Blood-Retinal Barrier: Role of the VEGF/uPAR Pathway.PloS one · 2017Article
- Thrombosis and Hemorrhage in Diabetic Retinopathy: A Perspective from an Inflammatory Standpoint.Seminars in thrombosis and hemostasis · 2015Review
- Levels of selected oxidative stress markers in the vitreous and serum of diabetic retinopathy patients.Molecular vision · 2015Article
- Ocular inflammation and endoplasmic reticulum stress are attenuated by supplementation with grape polyphenols in human retinal pigmented epithelium cells and in C57BL/6 mice.The Journal of nutrition · 2014Article
Corrections and comments
- Correction · 2017-10-16Duplication of/in Image · Investigation by Company/Institution · Investigation by Journal/Publisher · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author ·
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- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Diabetes-induced breakdown of the blood-retinal barrier (BRB) has been linked to hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and is likely mediated by an increase in oxidative stress. We have shown that VEGF increases permeability of retinal endothelial cells (REC) by inducing expression of urokinase plasminogen activator receptor (uPAR). The purpose of this study was to define the role of superoxide anion in VEGF/uPAR expression and BRB breakdown in diabetes. Studies were performed in streptozotocin diabetic rats and mice and high glucose (HG) treated REC. The superoxide dismutase (SOD) mimetic tempol blocked diabetes-induced permeability and uPAR expression in rats and the cell permeable SOD inhibited HG-induced expression of uPAR and VEGF in REC. Inhibiting VEGFR blocked HG-induced expression of VEGF and uPAR and GSK-3β phosphorylation in REC. HG caused β-catenin translocation from the plasma membrane into the cytosol and nucleus. Treatment with HG-conditioned media increased REC paracellular permeability that was blocked by anti-uPA or anti-uPAR antibodies. Moreover, deletion of uPAR blocked diabetes-induced BRB breakdown and activation of MMP-9 in mice. Together, these data indicate that diabetes-induced oxidative stress triggers BRB breakdown by a mechanism involving uPAR expression through VEGF-induced activation of the GSK3β/β-catenin signaling pathway.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.