ArticleEMBO molecular medicine2023
HIF2α activation and mitochondrial deficit due to iron chelation cause retinal atrophy.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Ferroptosis in retinal pigment epithelial cells: Current status and future developments.Indian journal of ophthalmology · 2026Review
- HIF2A as a prognostic and clinical therapeutic target in ovarian clear cell carcinoma.International journal of cancer · 2026Article
- Modulation of Iron-Induced Glucose Metabolic Reprogramming Alleviates Retinal Pigment Epithelial Cell Senescence.Investigative ophthalmology & visual science · 2026Article
- Disrupted energy metabolism is associated with retinal ganglion cell degeneration in autosomal dominant optic atrophy.Science advances · 2026Article
- Ferroptosis and retinal ganglion cell death in glaucoma: Mechanisms and therapeutic approaches.Journal of pharmaceutical analysis · 2026Review
- Steap4 Promotes Senile Osteoporosis via FeAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effects of different anesthetic drugs on electroretinography in mice.Scientific reports · 2025Article
- Ablating VHL in rod photoreceptors modulates RPE glycolysis and improves preclinical model of retinitis pigmentosa.The Journal of clinical investigation · 2025Article
- Ferroptosis in ocular diseases: mechanisms, crosstalk with other cell death pathways, and therapeutic prospects.Frontiers in medicine · 2025Review
- Why cells need iron: a compendium of iron utilisation.Trends in endocrinology and metabolism: TEM · 2024Review
- Pilot Study on the Effect of Patient Condition and Clinical Parameters on Hypoxia-Induced Factor Expression:International journal of molecular sciences · 2024Article
- Sex hormone binding globulin (SHBG) modulates mitochondrial dynamics in PPARγ-depleted equine adipose derived stromal cells.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Targeting miR-181a/b in retinitis pigmentosa: implications for disease progression and therapy.Cell & bioscience · 2024Article
- Medium Depth Influences O2 Availability and Metabolism in Human RPE Cultures.Investigative ophthalmology & visual science · 2023Article
- Nutritional Factors: Benefits in Glaucoma and Ophthalmologic Pathologies.Life (Basel, Switzerland) · 2023Review
- Lifting the iron curtain of vision.EMBO molecular medicine · 2023Article
- HIF2α activation and mitochondrial deficit due to iron chelation cause retinal atrophy.EMBO molecular medicine · 2023Article
- Modulation of Hypoxia-Inducible Factors and Vascular Endothelial Growth Factor Expressions by Superfood Camu-Camu (Journal of ophthalmology · 2023Article
- Iron overload and chelation modulates bisretinoid levels in the retina.Frontiers in ophthalmology · 2023Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Iron accumulation causes cell death and disrupts tissue functions, which necessitates chelation therapy to reduce iron overload. However, clinical utilization of deferoxamine (DFO), an iron chelator, has been documented to give rise to systemic adverse effects, including ocular toxicity. This study provided the pathogenic and molecular basis for DFO-related retinopathy and identified retinal pigment epithelium (RPE) as the target tissue in DFO-related retinopathy. Our modeling demonstrated the susceptibility of RPE to DFO compared with the neuroretina. Intriguingly, we established upregulation of hypoxia inducible factor (HIF) 2α and mitochondrial deficit as the most prominent pathogenesis underlying the RPE atrophy. Moreover, suppressing hyperactivity of HIF2α and preserving mitochondrial dysfunction by α-ketoglutarate (AKG) protects the RPE against lesions both in vitro and in vivo. This supported our observation that AKG supplementation alleviates visual impairment in a patient undergoing DFO-chelation therapy. Overall, our study established a significant role of iron deficiency in initiating DFO-related RPE atrophy. Inhibiting HIF2α and rescuing mitochondrial function by AKG protect RPE cells and can potentially ameliorate patients' visual function.
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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.