Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Degeneration
AbstractAging and oxidative stress seem to be the most important factors in the pathogenesis of age-related macular degeneration (AMD), a condition affecting many elderly people in the developed world. However, aging is associated with the accumulation of oxidative damage in many biomolecules, including DNA. Furthermore, mitochondria may be especially important in this process because the reactive oxygen species produced in their electron transport chain can damage cellular components. Therefore, the cellular response to DNA damage, expressed mainly through DNA repair, may play an important role in AMD etiology. In several studies the increase in mitochondrial DNA (mtDNA) damage and mutations, and the decrease in the efficacy of DNA repair have been correlated with the occurrence and the stage of AMD. It has also been shown that mitochondrial DNA accumulates more DNA lesions than nuclear DNA in AMD. However, the DNA damage response in mitochondria is executed by nucleus-encoded proteins, and thus mutagenesis in nuclear DNA (nDNA) may affect the ability to respond to mutagenesis in its mitochondrial counterpart. We reported that lymphocytes from AMD patients displayed a higher amount of total endogenous basal and oxidative DNA damage, exhibited a higher sensitivity to hydrogen peroxide and UV radiation, and repaired the lesions induced by these factors less effectively than did cells from control individuals. We postulate that poor efficacy of DNA repair (i.e., is impaired above average for a particular age) when combined with the enhanced sensitivity of retinal pigment epithelium cells to environmental stress factors, contributes to the pathogenesis of AMD. Collectively, these data suggest that the cellular response to both mitochondrial and nuclear DNA damage may play an important role in AMD pathogenesis.
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Blasiak, J.; Glowacki, S.; Kauppinen, A.; Kaarniranta, K. Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Degeneration. Int. J. Mol. Sci. 2013, 14, 2996-3010.
Blasiak J, Glowacki S, Kauppinen A, Kaarniranta K. Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Degeneration. International Journal of Molecular Sciences. 2013; 14(2):2996-3010.Chicago/Turabian Style
Blasiak, Janusz; Glowacki, Sylwester; Kauppinen, Anu; Kaarniranta, Kai. 2013. "Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Degeneration." Int. J. Mol. Sci. 14, no. 2: 2996-3010.