ArticleThe American journal of pathology2003
Experimental diabetes causes breakdown of the blood-retina barrier by a mechanism involving tyrosine nitration and increases in expression of vascular endothelial growth factor and urokinase plasminogen activator receptor.
Article in The American journal of pathology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 202 citations in OpenAlex.
- Role of NADPH Oxidases as Novel Therapeutic Targets for the Impaired Neurovascular Unit in the Early Stage of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Neuroprotection in Diabetes Retinal Disease: An Unmet Medical Need.International journal of molecular sciences · 2026Review
- Inhibiting the uPAR/FPR1 interactions reduces blood-retinal barrier breakdown and improves retinal function in a rat model of diabetes.Frontiers in neuroscience · 2026Article
- Endothelial function can be modulated by acute hyperglycemia.Scientific reports · 2025Article
- Oral Intake of Hydrogen Water Improves Retinal Blood Flow Dysregulation in Response to Flicker Stimulation and Systemic Hyperoxia in Diabetic Mice.Translational vision science & technology · 2024Article
- High Glucose Increases Lactate and Induces the Transforming Growth Factor Beta-Smad 1/5 Atherogenic Pathway in Primary Human Macrophages.Biomedicines · 2024Article
- Investigation of the Effects of a Novel NOX2 Inhibitor, GLX7013170, against Glutamate Excitotoxicity and Diabetes Insults in the Retina.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Effects of Nox4 upregulation on PECAM-1 expression in a mouse model of diabetic retinopathy.PloS one · 2024Article
- Article
- Wnt Signaling in Inner Blood-Retinal Barrier Maintenance.International journal of molecular sciences · 2021Review
- The stress response protein REDD1 as a causal factor for oxidative stress in diabetic retinopathy.Free radical biology & medicine · 2021Review
- Global assessment of arteriolar, venular and capillary changes in normal tension glaucoma.Scientific reports · 2020Article
- Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve: galectin-3 participation.Neural regeneration research · 2020Review
- A New Human Blood-Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes.International journal of molecular sciences · 2020Article
- Tangeretin Inhibition of High-Glucose-Induced IL-1Journal of diabetes research · 2020Article
- Bradykinin Type 1 Receptor - Inducible Nitric Oxide Synthase: A New Axis Implicated in Diabetic Retinopathy.Frontiers in pharmacology · 2019Article
- Colony-stimulating factor 1 receptor inhibition prevents disruption of the blood-retina barrier during chronic inflammation.Journal of neuroinflammation · 2018Article
- High Glucose-Mediated Tyrosine Nitration of PI3-Kinase: A Molecular Switch of Survival and Apoptosis in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2018Article
- Probucol prevents the attenuation of βNaunyn-Schmiedeberg's archives of pharmacology · 2017Article
- VEGF production and signaling in Müller glia are critical to modulating vascular function and neuronal integrity in diabetic retinopathy and hypoxic retinal vascular diseases.Vision research · 2017Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The purpose of these experiments was to determine the specific role of reactive oxygen species (ROS) in the blood-retinal barrier (BRB) breakdown that characterizes the early stages of vascular dysfunction in diabetes. Based on our data showing that high glucose increases nitric oxide, superoxide, and nitrotyrosine formation in retinal endothelial cells, we hypothesized that excess formation of ROS causes BRB breakdown in diabetes. Because ROS are known to induce increases in expression of the well-known endothelial mitogen and permeability factor vascular endothelial growth factor (VEGF) we also examined their influence on the expression of VEGF and its downstream target urokinase plasminogen activator receptor (uPAR). After 2 weeks of streptozotocin-induced diabetes, analysis of albumin leakage confirmed a prominent breakdown of the BRB. This permeability defect was correlated with significant increases in the formation of nitric oxide, lipid peroxides, and the peroxynitrite biomarker nitrotyrosine as well as with increases in the expression of VEGF and uPAR. Treatment with a nitric oxide synthase inhibitor (N-omega-nitro-L-arginine methyl ester, 50 mg/kg/day) or peroxynitrite scavenger (uric acid, 160 mg/kg/day) blocked the breakdown in the BRB and prevented the increases in formation of lipid peroxides and tyrosine nitration as well as the increases in expression of VEGF and uPAR. Taken together, these data indicate that early diabetes causes breakdown of the BRB by a mechanism involving the action of reactive nitrogen species in promoting expression of VEGF and uPAR.
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