Abstract |
Retinitis pigmentosa is a heterogeneous group of retinal degenerations characterized by a progressive loss of photoreceptors through the process of apoptosis. The apoptotic cell death of photoreceptors appears to represent a final common pathway in the pathology of retinitis pigmentosa. Previous studies have reported the ability of antioxidants to ameliorate light-induced retinal degeneration, suggesting a role for oxidative stress in photoreceptor cell death. This study demonstrates an early and sustained increase in intracellular reactive oxygen species accompanied by a rapid depletion of intracellular glutathione in an in vitro model of photoreceptor apoptosis. These early changes in the cellular redox state precede disruption of mitochondrial transmembrane potential, nuclear condensation, DNA nicking, and cell shrinkage, all of which are well-characterized events of apoptotic cell death. The ability of zinc chloride and pyrrolidine dithiocarbamate, two established antioxidants, to inhibit photoreceptor apoptosis through the scavenging of intracellular reactive oxygen species establishes a role for reactive oxygen species as possible mediators of in vitro photoreceptor apoptosis. This study provides a molecular basis for the inhibition of photoreceptor apoptosis by antioxidants.
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Authors | R J Carmody, A J McGowan, T G Cotter |
Journal | Experimental cell research
(Exp Cell Res)
Vol. 248
Issue 2
Pg. 520-30
(May 01 1999)
ISSN: 0014-4827 [Print] United States |
PMID | 10222143
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 1999 Academic Press. |
Chemical References |
- Antioxidants
- Free Radical Scavengers
- Peroxides
- Reactive Oxygen Species
- Glutathione
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Topics |
- Animals
- Antioxidants
(pharmacology)
- Apoptosis
- Free Radical Scavengers
(pharmacology)
- Glutathione
(metabolism)
- Membrane Potentials
- Mice
- Mice, Inbred C57BL
- Mitochondria
(metabolism)
- Peroxides
(metabolism)
- Photoreceptor Cells, Vertebrate
(drug effects, metabolism)
- Reactive Oxygen Species
(metabolism)
- Retina
(drug effects, metabolism)
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