ArticleInvestigative ophthalmology & visual science2010
Role of matrix metalloproteinase-9 in the development of diabetic retinopathy and its regulation by H-Ras.
Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 111 citations in OpenAlex.
- Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026Review
- Theophylline Inhibits Capillary Degeneration in Early Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Article
- A theoretical framework for extrapolating Andrographis paniculata mechanisms to the novel CIRDD and IROD diabetes clusters.Theory in biosciences = Theorie in den Biowissenschaften · 2026Article
- Comparative Tear Fluid Proteomics to Explore Treatment Responsiveness in Diabetic Macular Edema: A Pilot Study.Journal of proteome research · 2025Article
- Proteomic profiling reveals immunomodulatory role of IL-33 in ocular bacterial and fungal infections.Infection and immunity · 2025Article
- Applications of Matrix Metalloproteinase-9-Related Nanomedicines in Tumors and Vascular Diseases.Pharmaceutics · 2025Review
- The Role of Antioxidant Plant Extracts' Composition and Encapsulation in Dietary Supplements and Gemmo-Derivatives, as Safe Adjuvants in Metabolic and Age-Related Conditions: A Review.Pharmaceuticals (Basel, Switzerland) · 2024Review
- High glucose enhances the activation of NLRP3 inflammasome by ambient fine particulate matter in alveolar macrophages.Particle and fibre toxicology · 2023Article
- AAV-Mediated Expression of Human VEGF, TNF-α, and IL-6 Induces Retinal Pathology in Mice.Translational vision science & technology · 2021Article
- Diabetic Nephropathy - a Review of Risk Factors, Progression, Mechanism, and Dietary Management.Biomolecules & therapeutics · 2021Review
- Diabetes-related intestinal region-specific thickening of ganglionic basement membrane and regionally decreased matrix metalloproteinase 9 expression in myenteric ganglia.World journal of diabetes · 2021Article
- The Safety of Pharmacological and Surgical Treatment of Diabetes in Patients with Diabetic Retinopathy-A Review.Journal of clinical medicine · 2021Review
- Mechanistic dissection of diabetic retinopathy using the protein-metabolite interactome.Journal of diabetes and metabolic disorders · 2020Article
- Acute changes in the retina and central retinal artery with methamphetamine.Experimental eye research · 2020Article
- Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone.International journal of molecular sciences · 2020Article
- Homocysteine Disrupts Balance between MMP-9 and Its Tissue Inhibitor in Diabetic Retinopathy: The Role of DNA Methylation.International journal of molecular sciences · 2020Article
- Cysteine-based regulation of redox-sensitive Ras small GTPases.Redox biology · 2019Review
- Diabetes-mediated IL-17A enhances retinal inflammation, oxidative stress, and vascular permeability.Cellular immunology · 2019Article
- Can Epigenetics of Endothelial Dysfunction Represent the Key to Precision Medicine in Type 2 Diabetes Mellitus?International journal of molecular sciences · 2019Review
- Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy.International journal of nanomedicine · 2019Article
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1 author at 1 institution in 1 country.
Funding
Abstract
purposeDiabetes activates a small molecular weight G-protein, H-Ras, in the retina and its capillary cells, and H-Ras activation is implicated in the apoptosis of retinal capillary cells. Matrix metalloproteinase (MMP)-9 is regulated by H-Ras, and in diabetes its activation is associated with increased vascular permeability. The goal of this study was to investigate the role of sustained activation of MMP-9 in the pathogenesis of diabetic retinopathy and to illustrate the mechanism through which it is upregulated in diabetes.
methodsRetinal MMP-9 activation and its tissue inhibitor, TIMP-1, were quantified in streptozotocin-induced diabetic rats. Inhibition of H-Ras by simvastatin on diabetes-induced activation of H-Ras was evaluated. The mechanism by which diabetes regulates retinal MMP-9 was confirmed by determining the effect of genetic or pharmacologic regulation of H-Ras on its activation in retinal endothelial cells.
resultsIn rats, MMP-9 was activated and expression of TIMP-1 was decreased in the retina and its microvasculature at both 2 months and 12 months of diabetes. In retinal endothelial cells, high glucose activated MMP-9, and inhibition of its activation (by pharmacologic inhibitor or siRNA) ameliorated accelerated apoptosis. Inhibition of H-Ras, both in diabetic rats (simvastatin) and in isolated endothelial cells (H-Ras siRNA), abrogated the activation of MMP-9 and prevented the reduction of TIMP-1.
conclusionsHyperglycemia-induced activation of MMP-9 accelerates apoptosis of retinal capillary cells, a phenomenon that predicts the development of diabetic retinopathy, and the activation of MMP-9 is downstream of H-Ras. Characterizing the role of MMP-9 in the development of diabetic retinopathy will help explore novel molecular targets for future pharmacological interventions.
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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.