DNA damage and repair in age-related macular degeneration

Front Biosci (Landmark Ed). 2011 Jan 1;16:1291-301. doi: 10.2741/3789.

Abstract

Oxidative stress may play an important role in the pathogenesis of age-related macular degeneration (AMD). Mitochondria produce reactive oxygen species (ROS), which induce degenerative changes typical for AMD. Mitochondrial DNA (mtDNA) is targeted by ROS and it is considered to be more vulnerable to damage than nuclear DNA (nDNA) due to the impaired DNA repair system, lack of nucleosomal organization and close vicinity of mitochondrial oxidative chain. Some reports suggest the association between mtDNA damage and AMD. However, the metabolism of mtDNA is mainly determined by the expression of nDNA. Therefore, the extent of damage to mtDNA in retinal cells depends on the overall efficacy of nDNA repair, which decreases with age. We showed an association between nDNA damage and repair and AMD. Also well-recognized factors of AMD pathogenesis, age and smoking, may exert their effects through the DNA damage and repair. In conclusion, DNA damage and repair, both in mitochondrial and nuclear genome, may play an important role in the pathogenesis of AMD, and their mutual relationship in this disease needs further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / physiology
  • DNA Damage*
  • DNA Repair*
  • DNA, Mitochondrial / genetics
  • Humans
  • Macular Degeneration / genetics*
  • Macular Degeneration / physiopathology
  • Mitochondria / physiology
  • Oxidative Stress
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / physiopathology

Substances

  • DNA, Mitochondrial