Purchase this article with an account.
B. F. Godley, F. Q. Liang, Y.-Z. Wang, J. Cai, H. Lin, M. E. Boulton; Correlation of Mitochondrial DNA Damage With Progression of Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2199.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Central to the cellular aging process is that mitochondria have limited DNA repair capacity and play a critical role in apoptotic cell death. In this study, we test whether macular RPE cells exhibit more mitochondria DNA (mtDNA) damage than those of peripheral RPE cells in the aged human population and whether the extent of DNA damage correlates with the progression of age-related macular degeneration (AMD).
Macular and peripheral RPE cells were isolated and cultured from human donor eyes of different ages. Primary culture RPE cells were used to test mitochondrial redox function by the MTT assay and the extent of mtDNA damage assessed by quantitative PCR. In order to test the mtDNA repair capacity, cultured RPE cells were exposed to H2O2 and mtDNA repair monitored over 48 hours. To categorize the level of AMD for donors eyes from which the RPE cells had been isolated, high-resolution, stereoscopic, color digital images of post-dissected bare RPE layer were taken and assessed according to Minnesota Grading System (MGS).
Mitochondria redox function decreased significantly (p<0.05) in the macular RPE cells compared to peripheral RPE cells. The macular RPE cells exhibited greater mtDNA damage than those of peripheral RPE cells from human eyes greater than 65 years of age. Furthermore, the degree of reduction in the mtDNA repair capacity was greater in macular RPE cells than in the peripheral RPE cells. We observed a positive correlation between mtDNA damage and the degree of AMD. By contrast, the mtDNA repair capacity negatively correlated to the level of AMD.
The findings highlight the possibility that mtDNA damage may play an important role in the progression of AMD. This mitochondrial DNA damage is, at least partially, due to the dysfunction in the mtDNA repair system, which may serve as a potential target for pharmaceutical intervention in AMD.
This PDF is available to Subscribers Only