Mitochondria-derived reactive oxygen species mediate blue light-induced death of retinal pigment epithelial cells.
Throughout the lifetime of an individual, light is focused onto the retina. The resulting photooxidative stress can cause acute or chronic retinal damage. The pathogenesis of age-related macular degeneration (AMD), the leading cause of legal blindness in the developed world, involves oxidative stress and death of the retinal pigment epithelium (RPE) followed by death of the overlying photoreceptors. Evidence suggests that damage due to exposure to light plays a role in AMD and other age-related eye diseases. In this work a system for light-induced damage and death of the RPE, based on the human ARPE-19 cell line, was used. Induction of mitochondria-derived reactive oxygen species (ROS) is shown to play a critical role in the death of cells exposed to short-wavelength blue light (425 +/- 20 nm). ROS and cell death are blocked either by inhibiting the mitochondrial electron transport chain or by mitochondria-specific antioxidants. These results show that mitochondria are an important source of toxic oxygen radicals in blue light-exposed RPE cells and may indicate new approaches for treating AMD using mitochondria-targeted antioxidants.
King
Ayala
A
F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gottlieb
Eyal
E
Brooks
David G
DG
Murphy
Michael P
MP
Dunaief
Joshua L
JL
D000375:Aging / Q000528:radiation effects; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002460:Cell Line; D004579:Electron Transport; D006801:Humans; D008027:Light; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D018384:Oxidative Stress / Q000528:radiation effects; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species