Journal
EXPERIMENTAL EYE RESEARCH
Volume 81, Issue 6, Pages 742-750Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2005.04.017
Keywords
DNA polymerase gamma; DNA repair; light damage; mitochondria; 8-oxoguanine-DNA-glycosylase; neuroprotection
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Funding
- NEI NIH HHS [R01 EY05121] Funding Source: Medline
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Bright light triggers biphasic photoreceptor nuclear DNA fragmentation, suggesting a DNA-repair response (Invest Ophthalmol Vis Sci 43:3511; 2002; Adv Med Biol 533:229-240; Mot Neurobiol 28:111-122). Here, we demonstrate a remarkable increase in expression of the mitochondrial DNA-repair enzymes, DNA polymerase gamma and 8-oxoguanine-DNA-glycosylase, following bright light treatment in rats. DNA polymerase gamma and 8-oxoguanine, the product of guanine oxidation, were selectively localized in photoreceptor synaptic terminals only within the superior central retinal region, where most light damage occurred. All induced DNA polymerase gamma was localized in photoreceptor synaptic terminals after 5 hr of light exposure, despite the fact that most photoreceptor cell mitochondria are confined to the inner segments. The neuroprotective platelet-activating factor-receptor antagonist LAU-0901 decreased mitochondrial DNA polymerase gamma up-regulation, suggesting that its neuroprotective effect is exerted upstream from this event. During aging, the ability to repair damaged photoreceptor DNA greatly declines. Thus, DNA-repair enzymes such as polymerase gamma and 8-oxoguanine-DNA-glycosylase may provide novel pharmacologic targets to promote DNA repair and rescue photoreceptors in retinal degenerative diseases. (c) 2005 Elsevier Ltd. All rights reserved.
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