ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Digoxin inhibits retinal ischemia-induced HIF-1alpha expression and ocular neovascularization.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 114 citations in OpenAlex.
- Novel Therapeutic Approaches for Treatment of Diabetic Retinopathy and Age-Related Macular Degeneration.Vision (Basel, Switzerland) · 2025Review
- Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer.Cellular & molecular biology letters · 2025Review
- Role of Digoxin in Preventing Cigarette Smoke-Induced COPD via HIF-1α Inhibition in a Mouse Model.International journal of chronic obstructive pulmonary disease · 2025Article
- Retinal ischemic diseases and promising therapeutic molecular targets.Histology and histopathology · 2025Review
- RGD-Functionalized Ginsenoside Rg3 Liposomes for Alleviating Oxidative Stress and Choroidal Neovascularization in Age-Related Macular Degeneration.International journal of nanomedicine · 2025Article
- VEGF inhibition increases expression of HIF-regulated angiogenic genes by the RPE limiting the response of wet AMD eyes to aflibercept.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.Acta pharmacologica Sinica · 2024Article
- Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- HIF1α-dependent hypoxia response in myeloid cells requires IRE1α.Journal of neuroinflammation · 2023Article
- Effects of medications on hypoxia-inducible factor in the retina: A review.Clinical & experimental ophthalmology · 2023Review
- Article
- Spleen Tyrosine Kinase Contributes to Müller Glial Expression of Proangiogenic Cytokines in Diabetes.Investigative ophthalmology & visual science · 2022Article
- ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization.JCI insight · 2022Article
- Action Sites and Clinical Application of HIF-1α Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Human Retinal Organoids Provide a Suitable Tool for Toxicological Investigations: A Comprehensive Validation Using Drugs and Compounds Affecting the Retina.Stem cells translational medicine · 2022Article
- Comparative Analysis Reveals Novel Changes in Plasma Metabolites and Metabolomic Networks of Infants With Retinopathy of Prematurity.Investigative ophthalmology & visual science · 2022Article
- Retinal and Choroidal Vascular Diseases: Past, Present, and Future: The 2021 Proctor Lecture.Investigative ophthalmology & visual science · 2021Article
- HIF-1α and HIF-2α redundantly promote retinal neovascularization in patients with ischemic retinal disease.The Journal of clinical investigation · 2021Article
- An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor.Cancers · 2021Review
- A Fairy Chemical Suppresses Retinal Angiogenesis as a HIF Inhibitor.Biomolecules · 2020Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Digoxin and other cardiac glycosides inhibit hypoxia-inducible factor-1 (HIF-1) transcriptional activity in cultured cells and suppress tumor xenograft growth. We tested the hypothesis that digoxin reduces HIF-1 levels in ischemic tissue in vivo and suppresses neovascularization. Well-established murine models of ocular neovascularization were used to test our hypothesis. In mice with ischemic retinopathy, intraocular or intraperitoneal injection of digoxin markedly reduced retinal levels of HIF-1alpha protein and mRNAs encoding multiple hypoxia-regulated proangiogenic proteins and their receptors. Daily intraperitoneal injection of 2 mg/kg starting at postnatal day (P) 12 or a single intravitreous injection of 100 ng of digoxin at P12 reduced retinal neovascularization by >70% at P17. Digoxin also reduced the number of CXCR4(+) cells and F4/80(+) macrophages in ischemic retina and significantly reduced choroidal neovascularization at Bruch's membrane rupture sites. Digoxin suppresses retinal and choroidal neovascularization by reducing HIF-1alpha levels, which blocks several proangiogenic pathways. Since digoxin suppresses multiple pathways in addition to VEGF signaling, it may provide advantages over specific VEGF antagonists for treatment of patients with retinal and choroidal diseases complicated by neovascularization and/or excessive vascular permeability. It may also be useful for treatment of neovascular diseases in other tissues.
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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.