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

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 mitochondrial cytochrome c oxidase (complex IV) function and tested for protection by N-tert-butyl hydroxylamine (NtBHA), 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.

• Authors: Ludmila A Voloboueva, David W Killilea, Hani Atamna, Bruce N Ames
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 21 Issue 14 Pg. 4077-86 (Dec 2007) ISSN: 1530-6860 [Electronic] United States
• PMID: 17656467 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antioxidants
• Hydroxylamines
• Iron Chelating Agents
• N-tert-butylhydroxylamine
• Iron

Topics

• Aged
• Antioxidants (metabolism, pharmacology)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects)
• Humans
• Hydroxylamines (metabolism, pharmacology)
• Iron (metabolism)
• Iron Chelating Agents (metabolism, pharmacology)
• Iron Overload (metabolism, pathology, prevention & control)
• Macular Degeneration (drug therapy, metabolism)
• Mitochondria (drug effects, metabolism)
• Oxidative Stress (drug effects, physiology)
• Pigment Epithelium of Eye (drug effects, metabolism, pathology)
• Retina (cytology, drug effects, metabolism)