N‐tert‐butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration
Open accessAbstract
Age‐related macular degeneration (AMD) is the leading cause of severe visual impairment in the elderly in developed countries. AMD patients have elevated levels of iron within the retinal pigment epithelia (RPE), which may lead to oxidative damage to mitochondria, disruption of retinal metabolism, and vision impairment or loss. As a possible model for iron‐induced AMD, we investigated the effects of excess iron in cultured human fetal RPE cells on oxidant levels and mitochon‐drial cytochrome c oxidase (complex IV) function and tested for protection by N‐tert‐butyl hydroxylamine (Nt‐ BHA), a known mitochondrial antioxidant. RPE exposure to ferric ammonium citrate resulted in a time‐ and dose‐ dependent increase in intracellular iron, which increased oxidant production and decreased glutathione (GSH) levels and mitochondrial complex IV activity. NtBHA addition to iron‐overloaded RPE cells led to a reduction of intracellular iron content, oxidative stress, and partial restoration of complex IV activity and GSH content. NtBHA might be useful in AMD due to its potential to reduce oxidative stress, mitochondrial damage, and age‐ related iron accumulation, which may damage normal RPE function and lead to loss of vision.— Voloboueva, L. A., Killilea, D. W., Atamna, H., Ames, B. N. N‐tert‐butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration. FASEB J . 21, 4077–4086 (2007)
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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 [1330]
Iron chelation may help to reverse the process in age-related macular degeneration.
“iron chelation may help to reverse the process”
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Ferroptosis in retinal pigment epithelial cells: Current status and future developments
Liu, W., Li, W., Wang, D., Wu, P., Jiang, J., Liu, Z., & Chen, X. (2026) · Indian Journal of Ophthalmology · doi:10.4103/ijo.ijo_2875_25
- Authors
- Voloboueva, L. A., Killilea, D. W., Atamna, H., & Ames, B. N.
- Affiliations
- Children's Hospital Oakland Research Institute Nutrition and Metabolism Center Oakland California USA
- ORCID
- Killilea, David W.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2007-07-26
- Volume
- 21
- Issue
- 14
- Pages
- 4077-4086
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC2597693
- OpenAlex
- W2168682828
- Cited by
- 33
- References
- 75
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 1 · 2014: 1 · 2012: 2
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (EY-02205, R01EY002205, R37EY002205, R21EY016101)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- mitochondrial antioxidants, retinal pigment epithelium, iron overload, age-related macular degeneration, oxidative stress, mitochondrial complex IV, cytochrome c oxidase, glutathione, ferric ammonium citrate, intracellular iron accumulation
- MeSH terms
- Aged, Antioxidants, Cells, Cultured, Dose-Response Relationship, Drug, Epithelial Cells, Humans, Hydroxylamines, Iron, Iron Chelating Agents, Macular Degeneration, Mitochondria, Pigment Epithelium of Eye, Retina, Oxidative Stress, Iron Overload
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