ArticleProceedings of the National Academy of Sciences of the United States of America2013
Hypoxic retinal Muller cells promote vascular permeability by HIF-1-dependent up-regulation of angiopoietin-like 4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 160 citations in OpenAlex.
- The effects of Berberis vulgaris consumption on plasma levels of IGF-1, IGFBPs, PPAR-γ and the expression of angiogenic genes in women with benign breast disease: a randomized controlled clinical trial.BMC complementary and alternative medicine · 2019Trial
- Angiopoietin-Like 4 Induces Upregulation of VEGF and sVCAM1 Through JNK/c-Jun and JAK2/STAT5 Signaling Pathways.Investigative ophthalmology & visual science · 2026Article
- Sex-specific efficacy of curcumin-loaded nanoparticles and insulin for ocular-cardiac complications in type 2 diabetes mice.iScience · 2026Article
- Targeting the ANGPTL4/NRP1/ABL1/RAD51 axis reverses cisplatin resistance by impairing DNA damage repair in head and neck cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Understanding the Molecular Basis of Pathological Retinal Angiogenesis: Roles of Lipids, Non-Coding RNAs, and Cellular Crosstalk.Investigative ophthalmology & visual science · 2026Review
- 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
- Recent Investigations on Pathogenesis, Biomarkers, Epigenetics, and Emerging Therapeutic Strategies to Modulate Multiple Signaling Pathways in Diabetic Retinopathy.Journal of ophthalmology · 2026Review
- Review
- Early-stage diabetic retinopathy: gut-metabolic triggers, immune-neurodegeneration, and interventions.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Review
- Article
- ANGPTL4: A Comprehensive Review of 25 Years of Research.Cancers · 2025Review
- Inhibition of Endothelial HIF-1α by IDF-11774 Attenuates Retinal Neovascularization and Vascular Leakage.Investigative ophthalmology & visual science · 2025Article
- New Markers for the Assessment of Microvascular Complications in Patients with Metabolic Syndrome.Metabolites · 2025Review
- Preclinical Retinal Disease Models: Applications in Drug Development and Translational Research.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling.Nature communications · 2025Article
- Single-cell transcriptomic profiling of heart reveals ANGPTL4 linking fibroblasts and angiogenesis in heart failure with preserved ejection fraction.Journal of advanced research · 2025Article
- Adipose Factor ANGPTL4: Its Role in Aging Mechanisms and Associated Diseases.Clinical interventions in aging · 2025Review
- Aqueous humor adipokine profile of primary open angle glaucoma patients and cataract patients with or without metabolic disorders.International journal of ophthalmology · 2025Article
- Pemafibrate Induces a Low Level of PPARα Agonist-Stimulated mRNA Expression of ANGPTL4 in ARPE19 Cell.Bioengineering (Basel, Switzerland) · 2024Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Vision loss from ischemic retinopathies commonly results from the accumulation of fluid in the inner retina [macular edema (ME)]. Although the precise events that lead to the development of ME remain under debate, growing evidence supports a role for an ischemia-induced hyperpermeability state regulated, in part, by VEGF. Monthly treatment with anti-VEGF therapies is effective for the treatment of ME but results in a major improvement in vision in a minority of patients, underscoring the need to identify additional therapeutic targets. Using the oxygen-induced retinopathy mouse model for ischemic retinopathy, we provide evidence showing that hypoxic Müller cells promote vascular permeability by stabilizing hypoxia-inducible factor-1α (HIF-1α) and secreting angiogenic cytokines. Blocking HIF-1α translation with digoxin inhibits the promotion of endothelial cell permeability in vitro and retinal edema in vivo. Interestingly, Müller cells require HIF--but not VEGF--to promote vascular permeability, suggesting that other HIF-dependent factors may contribute to the development of ME. Using gene expression analysis, we identify angiopoietin-like 4 (ANGPTL4) as a cytokine up-regulated by HIF-1 in hypoxic Müller cells in vitro and the ischemic inner retina in vivo. ANGPTL4 is critical and sufficient to promote vessel permeability by hypoxic Müller cells. Immunohistochemical analysis of retinal tissue from patients with diabetic eye disease shows that HIF-1α and ANGPTL4 localize to ischemic Müller cells. Our results suggest that ANGPTL4 may play an important role in promoting vessel permeability in ischemic retinopathies and could be an important target for the treatment of ME.
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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.