The DOI matches its Crossref record; 150 of the 153 references it cites were found in a registry or an index.
Iron homeostasis and toxicity in retinal degeneration
Open accessAbstract
Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels buildup with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich's ataxia, and panthothenate kinase-associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age-matched controls. Over the past 10 years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter-1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron-regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including glaucoma, cataract, AMD, and conditions causing intraocular hemorrhage. While iron deficiency must be prevented, the therapeutic potential of limiting iron-induced ocular oxidative damage is high. Systemic, local, or topical iron chelation with an expanding repertoire of drugs has clinical potential.
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“Retinal iron levels increase with age [1322], iron is significantly implicated in AMD [1323-1329], and iron chelation may help to reverse the process [1330].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1328]
Citations
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The Retinal Pigment Epithelium in Health and Disease
Sparrrow, J. R., Hicks, D., & Hamel, C. (2010) · Current Molecular Medicine · doi:10.2174/156652410793937813 · Cited by 655
The dynamic nature of Bruch's membrane
Booij, J. C., Baas, D. C., Beisekeeva, J., Gorgels, T. G. M. F., & Bergen, A. A. B. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.08.003 · Cited by 581
Kell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554
Jung, T., Catalgol, B., & Grune, T. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2009.04.001 · Cited by 401
Mettu, P. S., Allingham, M. J., & Cousins, S. W. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100906 · Cited by 370
Metadata
- Authors
- He, X., Hahn, P., Iacovelli, J., Wong, R., King, C., Bhisitkul, R., Massaro-Giordano, M., & Dunaief, J. L.
- Affiliations
- University of Pennsylvania (US)
- University of California, San Francisco (US)
- Corresponding author
- Dunaief, Joshua L.
- Venue
- Progress in Retinal and Eye Research
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 26
- Issue
- 6
- Pages
- 649-673
- ISSN
- 1350-9462 (ISSN-L)
- PMC
- PMC2093950
- OpenAlex
- W2055021524
- Cited by
- 260
- References
- 153
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 18 · 2023: 17 · 2022: 18 · 2021: 19 · 2020: 20 · 2019: 14 · 2018: 15 · 2017: 13 · 2016: 10 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 17
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in Retinal and Eye Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (EY 015240, R01EY015240)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- iron homeostasis, retinal degeneration, iron toxicity, oxidative stress, hydroxyl radicals, age-related macular degeneration, ceruloplasmin, transferrin, aceruloplasminemia, Friedreich's ataxia, iron chelation, iron overload, glaucoma, cataract, intraocular hemorrhage
- MeSH terms
- Animals, Biological Transport, Epithelial Cells, Homeostasis, Humans, Iron, Lens, Crystalline, Retina, Retinal Degeneration, Oxidative Stress
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