ArticleDiabetes2013
VEGF secreted by hypoxic Müller cells induces MMP-2 expression and activity in endothelial cells to promote retinal neovascularization in proliferative diabetic retinopathy.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 132 citations in OpenAlex.
- Stage-dependent signaling networks and therapeutic strategies in diabetic retinopathy: from neurovascular dysfunction to angiogenesis and fibrosis.Molecular biology reports · 2026Review
- Associations between carotid macrovascular and retinal microvascular alterations in diabetes: Evidence synthesis and implications for risk assessment.Atherosclerosis plus · 2026Review
- Regulation of Glutathione Peroxidase 4 in Diabetic Retinopathy.International journal of molecular sciences · 2026Article
- Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026Review
- GABA Receptor Activation in Müller Glia as a Molecular Switch for Controlling VEGF-A in the Retina.ASN neuro · 2026Article
- Scavenging acrolein with 2-HDP preserves neurovascular integrity in a rat model of diabetic retinal disease.Diabetologia · 2025Article
- Diabetic Retinopathy, a Comprehensive Overview on Pathophysiology and Relevant Experimental Models.International journal of molecular sciences · 2025Review
- PRL3-zumab as an anti-angiogenic therapy in neovascular eye diseases.Nature communications · 2025Article
- Differential Effects of Retinol-Binding Protein 3 and Anti-VEGF Antibodies on Retinal Dysfunctions in Diabetic Retinopathy.Diabetes · 2025Article
- Doxycycline inhibits MMP-2 retinal activity and modulates the angiogenic processFrontiers in cell and developmental biology · 2025Article
- Role of exosome-derived miRNAs in diabetic wound angiogenesis.Molecular and cellular biochemistry · 2024Review
- Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinases explored in relation to the severity and progression of diabetic retinopathy in patients with type 1 diabetes: baseline and prospective analyses.BMJ open ophthalmology · 2024Article
- Müller Glial Cells in the Macula: Their Activation and Cell-Cell Interactions in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- Effects of aflibercept and bevacizumab on cell viability, cell metabolism and inflammation in hypoxic human Müller cells.PloS one · 2024Article
- Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.The Journal of clinical investigation · 2023Article
- Diet as a Source of Acrolein: Molecular Basis of Aldehyde Biological Activity in Diabetes and Digestive System Diseases.International journal of molecular sciences · 2023Review
- Protective Effect of NOCells · 2023Article
- Dual anti-angiogenic and anti-metastatic activity of myriocin synergistically enhances the anti-tumor activity of cisplatin.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- HIF-1α accumulation in response to transient hypoglycemia may worsen diabetic eye disease.Cell reports · 2023Article
- Mechanism underlying Müller cell pyroptosis and its role in the development of proliferative vitreoretinopathy.Clinics (Sao Paulo, Brazil) · 2023Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
In proliferative diabetic retinopathy (PDR), retinal ischemia promotes neovascularization (NV), which can lead to profound vision loss in diabetic patients. Treatment for PDR, panretinal photocoagulation, is inherently destructive and has significant visual consequences. Therapies targeting vascular endothelial growth factor (VEGF) have transformed the treatment of diabetic eye disease but have proven inadequate for treating NV, prompting exploration for additional therapeutic options for PDR patients. In this regard, extracellular proteolysis is an early and sustained activity strictly required for NV. Extracellular proteolysis in NV is facilitated by the dysregulated activity of matrix metalloproteinases (MMPs). Here, we set out to better understand the regulation of MMPs by ischemia in PDR. We demonstrate that accumulation of hypoxia-inducible factor-1α in Müller cells induces the expression of VEGF, which, in turn, promotes increased MMP-2 expression and activity in neighboring endothelial cells (ECs). MMP-2 expression was detected in ECs in retinal NV tissue from PDR patients, whereas MMP-2 protein levels were elevated in the aqueous of PDR patients compared with controls. Our findings demonstrate a complex interplay among hypoxic Müller cells, secreted angiogenic factors, and neighboring ECs in the regulation of MMP-2 in retinal NV and identify MMP-2 as a target for the treatment of PDR.
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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.