ArticleInvestigative ophthalmology & visual science2008
Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 120 citations in OpenAlex.
- ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS.Retina (Philadelphia, Pa.) · 2019Trial
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- Transferrin is a drug candidate for the treatment of dry age-related macular degeneration (AMD).Cell death & disease · 2025Article
- Dysregulation of Mitochondrial Iron Regulators as a Basis of Iron-Mediated Retinal Degeneration in Rats.Neurotoxicity research · 2025Article
- Oxidative Stress and Antioxidants in Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2023Review
- The biology of mammalian multi-copper ferroxidases.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- Cell Sources for Retinal Regeneration: Implication for Data Translation in Biomedicine of the Eye.Cells · 2022Review
- Ferroptosis as a mechanism of non-ferrous metal toxicity.Archives of toxicology · 2022Review
- Conditional knockout of hephaestin in the neural retina disrupts retinal iron homeostasis.Experimental eye research · 2022Article
- A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation.Journal of neurochemistry · 2022Article
- The retinal pigment epithelium: Development, injury responses, and regenerative potential in mammalian and non-mammalian systems.Progress in retinal and eye research · 2021Review
- Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia.Aging cell · 2021Article
- Release of Iron-Loaded Ferritin in Sodium Iodate-Induced Model of Age Related Macular Degeneration: An In-Vitro and In-Vivo Study.Antioxidants (Basel, Switzerland) · 2021Article
- Single-cell RNA sequencing in vision research: Insights into human retinal health and disease.Progress in retinal and eye research · 2021Review
- Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration.Aging and disease · 2021Review
- Effects of Excess Iron on the Retina: Insights From Clinical Cases and Animal Models of Iron Disorders.Frontiers in neuroscience · 2021Review
- Bull's eye maculopathy associated with hereditary hemochromatosis.American journal of ophthalmology case reports · 2020Article
- Oral administration of the iron chelator deferiprone protects against loss of retinal ganglion cells in a mouse model of glaucoma.Experimental eye research · 2020Article
- SPECKLED HYPOAUTOFLUORESCENCE AS A SIGN OF RESOLVED SUBRETINAL HEMORRHAGE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.Retina (Philadelphia, Pa.) · 2019Article
- Liver-Specific, but Not Retina-Specific, Hepcidin Knockout Causes Retinal Iron Accumulation and Degeneration.The American journal of pathology · 2019Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
purposeIron is an essential element in human metabolism but also is a potent generator of oxidative damage with levels that increase with age. Several studies suggest that iron accumulation may be a factor in age-related macular degeneration (AMD). In prior studies, both iron overload and features of AMD were identified in mice deficient in the ferroxidase ceruloplasmin (Cp) and its homologue hephaestin (Heph) (double knockout, DKO). In this study, the location and timing of iron accumulation, the rate and reproducibility of retinal degeneration, and the roles of oxidative stress and complement activation were determined.
methodsMorphologic analysis and histochemical iron detection by Perls' staining was performed on retina sections from DKO and control mice. Immunofluorescence and immunohistochemistry were performed with antibodies detecting activated complement factor C3, transferrin receptor, L-ferritin, and macrophages. Tissue iron levels were measured by atomic absorption spectrophotometry. Isoprostane F2alpha-VI, a specific marker of oxidative stress, was quantified in the tissue by gas chromatography/mass spectrometry.
resultsDKOs exhibited highly reproducible age-dependent iron overload, which plateaued at 6 months of age, with subsequent progressive retinal degeneration continuing to at least 12 months. The degeneration shared some features of AMD, including RPE hypertrophy and hyperplasia, photoreceptor degeneration, subretinal neovascularization, RPE lipofuscin accumulation, oxidative stress, and complement activation.
conclusionsDKOs have age-dependent iron accumulation followed by retinal degeneration modeling some of the morphologic and molecular features of AMD. Therefore, these mice are a good platform on which to test therapeutic agents for AMD, such as antioxidants, iron chelators, and antiangiogenic agents.
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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.