May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Age–related photoreceptor DNA repair
Author Affiliations & Notes
  • B. Mathew
    Ophthalmology/Neuroscience, Louisiana Sate University Health Sciences Center, New Orleans, LA
  • W.C. Gordon
    Ophthalmology/Neuroscience, Louisiana Sate University Health Sciences Center, New Orleans, LA
  • M.S. Cortina
    Ophthalmology/Neuroscience, Louisiana Sate University Health Sciences Center, New Orleans, LA
  • D.R. Bergsma
    Ophthalmology/Neuroscience, Louisiana Sate University Health Sciences Center, New Orleans, LA
  • W.J. Lukiw
    Ophthalmology/Neuroscience, Louisiana Sate University Health Sciences Center, New Orleans, LA
  • N.G. Bazan
    Ophthalmology/Neuroscience, Louisiana Sate University Health Sciences Center, New Orleans, LA
  • Footnotes
    Commercial Relationships  B. Mathew, None; W.C. Gordon, None; M.S. Cortina, None; D.R. Bergsma, None; W.J. Lukiw, None; N.G. Bazan, None.
  • Footnotes
    Support  NIH Grant R01EY05121, Neurobiotech Program LA
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 772. doi:
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      B. Mathew, W.C. Gordon, M.S. Cortina, D.R. Bergsma, W.J. Lukiw, N.G. Bazan; Age–related photoreceptor DNA repair . Invest. Ophthalmol. Vis. Sci. 2004;45(13):772.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Photoreceptors are endowed with in–house DNA repair triggered by exposure to bright light. DNA lesions in mitochondria result from base excision. The main mechanism for repair involves MtDNA polymerase γ, while DNA polymerase ß is the primary enzyme in nDNA repair. In photoreceptor cells, DNA polymerase γ is maximally induced first at 6h after light in response to mtDNA damage. Induction of DNA polymerase ß coincides with the peak of nDNA fragmentation 24h after light. Activity of DNA polymerase γ and ß decreases in aging which may contribute to age–related retinal degenerations. The purpose of this study is to define how aging affects photoreceptor DNA repair mediated by these two enzymes. Methods: 1, 2.5, 5, and 10–month–old Sprague Dawley rats, dark adapted for 2 days, were light–treated for 5h, returned to darkness, and killed 6 and 24h later. Control animals were maintained in darkness until sacrificed. Retinas were collected and analyzed by Western blot. DNA polymerase γ and ß were quantified for each age group. Immunohistochemistry in frozen sections was performed for the localization of DNA polymerase γ and ß. Results: Western blot analysis showed a decline in light–induced upregulation of both repair enzymes as a function of age. DNA polymerase γ showed a 50% decrease in 10–month–old compared to 1 and 2.5–month–old animals, while DNA polymerase ß demonstrated a 60% decrease. Conclusions: The upregulation of DNA polymerase γ and ß following light damage decreases with age. The decreased ability of photoreceptor DNA repair may contribute to accumulation of deleterious mutations in mtDNA as well as nDNA which, in turn, leads to photoreceptor cell damage. Deterioration of DNA repair signaling with age may be a major contributing factor in the development of age–related macular degeneration.

Keywords: aging • mitochondria • photoreceptors 
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