ArticleAging cell2021
Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia.
Article in Aging cell, 2021. 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, 45 citations in OpenAlex.
- Ferroptosis in retinal pigment epithelial cells: Current status and future developments.Indian journal of ophthalmology · 2026Review
- Photoreceptor Vulnerability to Ferroptosis: Membrane Phospholipid Peroxidation, Mitochondrial Homeostasis, and RPE-Photoreceptor Coupling.Current issues in molecular biology · 2026Review
- Modulation of Iron-Induced Glucose Metabolic Reprogramming Alleviates Retinal Pigment Epithelial Cell Senescence.Investigative ophthalmology & visual science · 2026Article
- Ferroptosis in diabetic retinopathy: cellular heterogeneity, progression, and therapeutic targets.Molecular biology reports · 2026Review
- The contribution of ferroptosis to the epithelial-mesenchymal transition phenotype in models of age-related macular degeneration.Frontiers in cell and developmental biology · 2026Article
- Ferroptosis and the eye: bridging the gap between cell death and vision preservation.Frontiers in immunology · 2026Review
- Ferrostatin-1, a ferroptosis inhibitor, mitigates all-trans-retinal-induced retinal pigment epithelium degeneration in mice.Journal of translational medicine · 2025Article
- Transferrin is a drug candidate for the treatment of dry age-related macular degeneration (AMD).Cell death & disease · 2025Article
- Bisretinoid lipofuscin, fundus autofluorescence and retinal disease.Progress in retinal and eye research · 2025Review
- PHOSPHO1 Suppresses Ferroptosis in Retinal Pigment Epithelial Cells by Reducing the Levels of Phosphatidylethanolamine Molecular Species.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Features that distinguish age-related macular degeneration from aging.Experimental eye research · 2025Review
- DNA-Dependent Protein Kinase Catalytic Subunit Prevents Ferroptosis in Retinal Pigment Epithelial Cells.Investigative ophthalmology & visual science · 2025Article
- Systemic Sodium Iodate Injection as a Model for Expanding Geographic Atrophy.Translational vision science & technology · 2025Article
- Activation of GSDME by all-International journal of biological sciences · 2025Article
- Serum Iron Status and Retinal Degenerative Diseases: A Mendelian Randomization Study on AMD, RP, and DR.Nutrients · 2024Article
- Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases.Cell death & disease · 2024Review
- Age-Related Macular Degeneration and Mitochondria-Associated Autoantibodies: A Review of the Specific Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Ferroptosis: a novel mechanism of cell death in ophthalmic conditions.Frontiers in immunology · 2024Review
- Inhibition of ferroptosis by POLE2 in gastric cancer cells involves the activation of NRF2/GPX4 pathway.Journal of cellular and molecular medicine · 2024Article
- Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Iron has been implicated in the pathogenesis of age-related retinal diseases, including age-related macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria-rich region, 4 h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all-trans-retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline-injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD-associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti-inflammatory medications, and choroidal neovascularization inhibitors.
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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.