Maculas Affected by Age-Related Macular Degeneration Contain Increased Chelatable Iron in the Retinal Pigment Epithelium and Bruch's Membrane
Abstract
OBJECTIVE: To investigate whether iron is involved in the pathogenesis of age-related macular degeneration (AMD). METHODS: Postmortem AMD-affected (nonexudative or exudative) and healthy maculas were studied using the 3,3'-diaminobenzidine-enhanced Perls Prussian blue stain. The Perls Prussian blue stain was quantified by computer-assisted analysis of digital images. To determine whether the iron was chelatable, sections treated with the iron chelator deferoxamine were compared with adjacent, nonchelated sections. RESULTS: Compared with healthy maculas, AMD-affected maculas had statistically significant increases in the total iron level. Some of this iron was chelatable. The iron was present in retinal pigment epithelium and Bruch's membrane in maculas from patients who had drusen only, geographic atrophy, and exudative AMD in pathologic areas and, occasionally, in relatively healthy areas. CONCLUSIONS: Oxidative stress has been implicated in the pathogenesis of AMD by the Age-Related Eye Disease Study. Increased concentrations of iron, which generate highly reactive hydroxyl radicals via the Fenton reaction, may induce oxidative stress in the macula and lead to AMD. As the increased iron concentrations in AMD-affected eyes consist in part of a chelatable iron pool, treatment of patients who have AMD with iron chelators might be considered a potential therapy. While there are, as yet, no clinical data indicating that the treatment of patients who have AMD with iron chelators is beneficial, data presented herein indicate that further investigation of iron concentrations in postmortem tissues and the mechanisms of iron transport in the retina is warranted.
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Retinal iron levels increase with age, iron is significantly implicated in AMD, and iron chelation may help to reverse the process.
“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 [1325]
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- Authors
- Hahn, P.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Hahn, Paul
- ORCID
- Hahn, Paul
- Venue
- Archives of Ophthalmology
- Publisher
- American Medical Association (AMA)
- Published
- 2003-08-01
- Volume
- 121
- Issue
- 8
- Pages
- 1099
- ISSN
- 0003-9950 (ISSN-L)
- OpenAlex
- W2123554280
- Cited by
- 258
- References
- 23
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 9 · 2023: 8 · 2022: 19 · 2021: 8 · 2020: 20 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 12 · 2014: 10 · 2013: 9 · 2012: 22
- FWCI
- 9.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (EY00417)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- age-related macular degeneration, iron, retinal pigment epithelium, Bruch's membrane, oxidative stress, Fenton reaction, hydroxyl radicals, deferoxamine, iron chelators, drusen, geographic atrophy, neovascular age-related macular degeneration, macula
- MeSH terms
- Aged, Aged, 80 and over, Deferoxamine, Female, Humans, Iron, Iron Chelating Agents, Macula Lutea, Macular Degeneration, Male, Pigment Epithelium of Eye, Prussian Blue Reaction, 3,3'-Diaminobenzidine, Bruch Membrane
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