ArticleInvestigative ophthalmology & visual science2011
Novel role of mitochondrial matrix metalloproteinase-2 in the development of diabetic retinopathy.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 92 citations in OpenAlex.
- Mitochondrial transfer: a novel paradigm for wound healing.Burns & trauma · 2026Review
- siRNA-mediated inhibition of NTT-MMP-2 reduces oxidative stress and apoptotic signaling in an ex vivo model of ischemia/reperfusion injury.Scientific reports · 2025Article
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- Oxidative stress and retinopathy: evidence from epidemiological studies.Journal of translational medicine · 2025Article
- Role of Tau Protein Hyperphosphorylation in Diabetic Retinal Neurodegeneration.Journal of ophthalmology · 2025Review
- Vitamin A, D, E, and K as Matrix Metalloproteinase-2/9 Regulators That Affect Expression and Enzymatic Activity.International journal of molecular sciences · 2023Review
- Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease.International journal of molecular sciences · 2023Review
- Chronic heat stress induces the expression ofFrontiers in genetics · 2023Article
- Research Progress on Mitochondrial Dysfunction in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2022Review
- Connexins and Glucose Metabolism in Cancer.International journal of molecular sciences · 2022Review
- Review
- Connexin 43 in Mitochondria: What Do We Really Know About Its Function?Frontiers in physiology · 2022Review
- The Role of Connexin in Ophthalmic Neovascularization and the Interaction between Connexin and Proangiogenic Factors.Journal of ophthalmology · 2022Review
- Therapeutic potential of curcumin in diabetic retinopathy (Review).International journal of molecular medicine · 2021Review
- An Update on Connexin Gap Junction and Hemichannels in Diabetic Retinopathy.International journal of molecular sciences · 2021Review
- Hydrogen Sulfide: A Potential Therapeutic Target in the Development of Diabetic Retinopathy.Investigative ophthalmology & visual science · 2020Article
- The Protective Effects of Flavonoids in Cataract Formation through the Activation of Nrf2 and the Inhibition of MMP-9.Nutrients · 2020Review
- Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications.Redox biology · 2020Review
- Extracellular Vesicles and MicroRNA: Putative Role in Diagnosis and Treatment of Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2020Review
- Homocysteine Disrupts Balance between MMP-9 and Its Tissue Inhibitor in Diabetic Retinopathy: The Role of DNA Methylation.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIn the pathogenesis of diabetic retinopathy, retinal mitochondria become dysfunctional, their DNA is damaged, and capillary cells undergo accelerated apoptosis. Matrix metalloproteinase-2 (MMP2) becomes activated and proapoptotic, and the therapies that inhibit the development of diabetic retinopathy alleviate MMP2 activation. The authors sought to elucidate the possible mechanism by which activated MMP2 contributes to mitochondrial dysfunction.
methodsThe effect of the regulation of MMP2 on mitochondrial dysfunction and the subcellular localization of the molecular chaperone important for mitochondrial integrity (Hsp60) and gap junction protein connexin 43 were investigated in retinal endothelial cells. The results were confirmed in retinal mitochondria isolated from diabetic mouse overexpressing MnSOD and in the retinas of normal rats that received intravitreal administration of MMP2.
resultsHigh glucose increased MMP2 and decreased connexin 43 in the mitochondria of retinal endothelial cells. Although the Hsp60 gene transcript was increased, its abundance in the mitochondria was decreased, and its interaction with MMP2 was increased. In mice, the overexpression of MnSOD protected retinal mitochondria from diabetes-induced increases in MMP2 and decreases in Hsp60 and connexin 43. MMP2 administration in normal rats damaged the retinal mitochondria, decreased Hsp60 and connexin 43, and accelerated the apoptosis of retinal capillary cells.
conclusionsElevated MMP2 in the mitochondria degrades its membranes by modulating Hsp60 and damaging connexin 43, and this activates the apoptotic machinery. Better understanding of MMP2-mediated mitochondrial damage could help identify new strategies for the treatment of this blinding disease.
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