ArticleProceedings of the National Academy of Sciences of the United States of America2023
Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 41 citations in OpenAlex.
- Protective role of aldehyde dehydrogenase 2 in retinal pigment epithelium cells with CoCl₂-induced hypoxic injury: an in-vitro study.BMC pharmacology & toxicology · 2026Article
- The Molecular Basis of Ocular Aging: Mechanisms, Pathologies, and Emerging Therapeutics.Investigative ophthalmology & visual science · 2026Review
- Protective Role of Erzhi Pills in HBiochemical genetics · 2026Article
- Mapping the Hypoxic Fitness Landscape of Retinal Pigment Epithelial Cells.International journal of molecular sciences · 2026Article
- Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026Review
- From environmental exposure to retinal pathology: epidemiological and mechanistic insights into multi-metal driven ocular diseases.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Retinal pigment epithelium pathology in age-related macular degeneration: mitigation with melatonin.Frontiers in medicine · 2026Review
- Eriocitrin inhibits sodium iodate-induced cuproptosis and barrier function impairment in retinal pigment epithelium via SIRT7/YAP/ATP7A pathway.Journal of translational medicine · 2025Article
- Characteristics of Retinal Oxygen Kinetics and Blood Flow in Myopia of Different Degrees.Investigative ophthalmology & visual science · 2025Article
- Association of Mesopic and Dark-Adapted Retinal Sensitivity With Type 1 Macular Neovascularization in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2025Article
- Ophthalmic formulation of methotrexate: a strategy of using the self-assembled LacAC4A nanoparticles for non-invasive drug delivery to the ocular posterior segment.Drug delivery · 2025Article
- Clinical characteristics and treatment outcomes of bilateral myopic macular neovascularization in high myopic patients.Acta ophthalmologica · 2025Article
- Lactate-binding protein DNMT3A in HRMECs promotes angiogenesis by upregulating VEGFA through HIF-1α lactylation.Genome biology · 2025Article
- Hesperidin and Hesperetin from Orange Peel Water Extract Protect against NaIOJournal of agricultural and food chemistry · 2025Article
- HIF1 activity in photoreceptors drives type 3 neovascularization and retinal atrophy in a new mouse model of age-related macular degeneration.Cell death & disease · 2025Article
- Na-Cl Cotransporter (SLC12A3) Inhibition Exacerbates Age-Related Macular Degeneration Via the Nrf2/HO-1 Ferroptosis Pathway.Investigative ophthalmology & visual science · 2025Article
- Green nanoscience for healthcare: Advancing biomedical innovation through eco-synthesized nanoparticle.Biotechnology reports (Amsterdam, Netherlands) · 2025Review
- OBM1701 Alleviates Choroidal Neovascularization in Experimental Animals Via Suppressing the Expression of HIF-1α in Retinal Pigment Epithelial Cells.Translational vision science & technology · 2025Article
- Feedback regulation between histone lactylation and ALKBH3-mediated glycolysis regulates age-related macular degeneration pathology.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced-while HIF-1 augmentation reduced-photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1α in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1α expression in photoreceptors contributes to the development of GA.
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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.