Cited by 33Retinal Diseases and TreatmentsAntioxidant Activity and Oxidative StressRetinal Development and Disorders

N‐tert‐butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration

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Voloboueva, Ludmila A., Killilea, David W., Atamna, Hani, Ames, Bruce N.·2007·The FASEB Journal

Abstract

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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Crossref · 10.1096/fj.07-8396com

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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
Venue
The FASEB Journal
Publisher
Wiley
Published
2007-07-26
Volume
21
Issue
14
Pages
4077-4086
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
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
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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