ArticleJournal of molecular medicine (Berlin, Germany)2017
The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization.
Article in Journal of molecular medicine (Berlin, Germany), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026Review
- Role of oxygen sensing and hypoxia-inducible factors in orchestrating innate immune responses.Nature immunology · 2025Review
- Dual Inhibition of HIF-1α and HIF-2α as a Promising Treatment for VHL-Associated Hemangioblastomas: A Pilot Study Using Patient-Derived Primary Cell Cultures.Biomedicines · 2025Article
- 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
- Retinal ischemic diseases and promising therapeutic molecular targets.Histology and histopathology · 2025Review
- 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
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Suprachoroidal Injection: A Novel Approach for Targeted Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.The Journal of clinical investigation · 2023Article
- HIF1α-dependent hypoxia response in myeloid cells requires IRE1α.Journal of neuroinflammation · 2023Article
- Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization.BMC genomics · 2023Article
- Article
- Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis.Frontiers in immunology · 2023Article
- HIF1 inhibitor acriflavine rescues early-onset preeclampsia phenotype in mice lacking placental prolyl hydroxylase domain protein 2.JCI insight · 2022Article
- Comparative Analysis Reveals Novel Changes in Plasma Metabolites and Metabolomic Networks of Infants With Retinopathy of Prematurity.Investigative ophthalmology & visual science · 2022Article
- Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms.Animal models and experimental medicine · 2021Review
- Retinal and Choroidal Vascular Diseases: Past, Present, and Future: The 2021 Proctor Lecture.Investigative ophthalmology & visual science · 2021Article
- An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor.Cancers · 2021Review
- Suprachoroidal Delivery of Small Molecules, Nanoparticles, Gene and Cell Therapies for Ocular Diseases.Pharmaceutics · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Acriflavine, a fluorescent drug previously used for bacterial and trypanosomal infections, reduces hypoxia-inducible factor-1 (HIF-1) and HIF-2 transcriptional activity. In mice with oxygen-induced ischemic retinopathy, intraocular or intraperitoneal injections of acriflavine caused dose-dependent suppression of retinal neovascularization (NV) and significantly reduced expression of HIF-1-responsive genes. Intraocular injection of 100 ng caused inner retina fluorescence within 1 h that was seen throughout the entire retina between 1 and 5 days, and at 7 days after injection, strongly suppressed choroidal NV at Bruch's membrane rupture sites. After suprachoroidal injection of 300 ng in rats, there was retinal fluorescence in the quadrant of the injection at 1 h that spread throughout the entire retina and choroid by 1 day, was detectable for 5 days, and dramatically reduced choroidal NV 14 days after rupture of Bruch's membrane. After topical administration of acriflavine in mice, fluorescence was seen in the retina and retinal pigmented epithelium within 5 min and was detectable for 6-12 h. Administration of 0.5% drops to the cornea twice a day significantly reduced choroidal NV in mice. Electroretinographic b-wave amplitudes were normal 7 days after intravitreous injection of 100 ng of acriflavine in mice, showed mild threshold reductions at highest stimulus intensities after injection of 250 ng, and more extensive changes after injection of 500 ng. These data provide additional evidence for an important role for HIF-1 in retinal and choroidal NV and suggest that acriflavine can target HIF-1 through a variety of modes of administration and has good potential to provide a novel therapy for retinal and choroidal vascular diseases. KEY MESSAGE: Acriflavine, an inhibitor of HIF-1, suppresses retinal and choroidal neovascularization. HIF-1 plays a critical role in ocular neovascularization. Acriflavine's fluorescence provides a mean to track its entry and exit from the retina. Acriflavine has therapeutic potential for the treatment of ocular neovascularization.
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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.