ArticleDiabetologia2011
Ischaemia-induced retinal neovascularisation and diabetic retinopathy in mice with conditional knockout of hypoxia-inducible factor-1 in retinal Müller cells.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 143 citations in OpenAlex.
- Glycohypoxia: a hypothesis linking chronic hyperglycemia to functional hypoxia and diabetic complications in type 2 diabetes.Medical gas research · 2026Review
- Navigating Anemia Therapy in CKD With Hypoxia-Inducible Factor Activators: A Review.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2026Review
- Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026Review
- Understanding the Molecular Basis of Pathological Retinal Angiogenesis: Roles of Lipids, Non-Coding RNAs, and Cellular Crosstalk.Investigative ophthalmology & visual science · 2026Review
- Imaging Hypoxia in the Diabetic Retina: A Potential Early-Detection Imaging Biomarker Before Detectable Retinopathy in Diabetes.Diabetes · 2026Article
- Ginger-Derived Nanoparticles Deliver a VEGFA-Targeting DNAzyme and Modulate Retinal VEGFA Expression and Inflammatory Markers in Experimental Diabetic Retinopathy.International journal of nanomedicine · 2026Article
- Ferroptosis-Mediated Cell-Specific Damage: Molecular Cascades and Therapeutic Breakthroughs in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2025Review
- Nrf2 Deficiency in Müller Cells Exacerbates Pathological Neovascularization in Ischemic Retinopathy.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Mechanisms Underlying Myopia Progression from Visual Signaling to Metabolic Remodeling in Retina.JMA journal · 2025Review
- Preclinical Retinal Disease Models: Applications in Drug Development and Translational Research.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Exploration Progress on Inflammatory Responses and Immune Regulatory Mechanisms in Diabetic Retinopathy.Journal of inflammation research · 2025Review
- Hypoxia-inducible factor activators: a novel class of oral drugs for the treatment of anemia of chronic kidney disease.Hematology. American Society of Hematology. Education Program · 2024Review
- Recent Insights into Roles of Hypoxia-Inducible Factors in Retinal Diseases.International journal of molecular sciences · 2024Review
- Characterization of the angiomodulatory effects of Interleukin 11 cis- and trans-signaling in the retina.Journal of neuroinflammation · 2024Article
- Targeting the Mitochondrial Chaperone TRAP1 Alleviates Vascular Pathologies in Ischemic Retinopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Redox Balance in Type 2 Diabetes: Therapeutic Potential and the Challenge of Antioxidant-Based Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Diabetic complications and prospective immunotherapy.Frontiers in immunology · 2023Review
- Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor.International journal of molecular sciences · 2022Article
- Spleen Tyrosine Kinase Contributes to Müller Glial Expression of Proangiogenic Cytokines in Diabetes.Investigative ophthalmology & visual science · 2022Article
- Amelioration of endothelial dysfunction by sodium glucose co-transporter 2 inhibitors: pieces of the puzzle explaining their cardiovascular protection.British journal of pharmacology · 2022Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
aims/hypothesisRetinal Müller cells are known to produce inflammatory and angiogenic cytokines, which play important roles in diabetic retinopathy. Hypoxia-inducible factor (HIF)-1 has been shown to play a crucial role in retinal inflammation and neovascularisation. We sought to determine the role of Müller cell-derived HIF-1 in oxygen-induced retinopathy (OIR) and diabetic retinopathy using conditional Hif-1α (also known as Hif1a) knockout (KO) mice.
methodsConditional Hif-1α KO mice were generated by crossing mice expressing cyclisation recombinase (cre, also known as P1_gp003) in Müller cells with floxed Hif-1α mice and used for OIR and streptozotocin-induced diabetes to induce retinal neovascularisation and inflammation, respectively. Abundance of HIF-1α and pro-angiogenic and pro-inflammatory factors was measured by immunoblotting and immunohistochemistry. Retinal neovascularisation was visualised by angiography and quantified by counting pre-retinal nuclei. Retinal inflammation was evaluated by leucostasis and vascular leakage.
resultsWhile the Hif-1α KO mice showed significantly decreased HIF-1α levels in the retina, they exhibited no apparent histological or visual functional abnormalities under normal conditions. Compared with wild-type counterparts, Hif-1α KO mice with OIR demonstrated attenuated overproduction of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM)-1, reduced vascular leakage and alleviated neovascularisation in the retina. Under diabetes conditions, disruption of Hif-1α in Müller cells attenuated the increases of retinal vascular leakage and adherent leucocytes, as well as the overproduction of VEGF and ICAM-1. CONCLUSIONS/
interpretationMüller cell-derived HIF-1α is a key mediator of retinal neovascularisation, vascular leakage and inflammation, the major pathological changes in diabetic retinopathy. Müller cell-derived HIF-1α is therefore a promising therapeutic target for diabetic retinopathy.
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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.