Lower Mitochondrial Copy Number Correlates with Risk of Age-Related Macular Degeneration
Lower mitochondrial copy number, meaning fewer copies of mitochondrial DNA and thus presumably fewer mitochondria in a cell, is here shown to correlate with the presence of age-related macular degeneration in older individuals. Mitochondrial copy number is one approach to measuring the degree of mitochondrial dysfunction present in tissues. In the study here, it is assessed in blood samples, and is thus a measure of the health of immune cells, the degree to which they are impacted by processes of aging. Many aspects of aging tend to correlate with one another, as aging emerges from a web of various forms of damage and dysfunction that all influence one another, so one can't draw conclusions about the degree to which mitochondrial dysfunction contributes to the development of age-related macular degeneration based on this data.
Mitochondrial dysfunction is a common occurrence in the aging process and is observed in diseases such as age-related macular degeneration (AMD). Increased levels of reactive oxygen species lead to damaged mitochondrial DNA (mtDNA), resulting in dysfunctional mitochondria, and, consequently, mtDNA causes further harm in the retinal tissue. However, it is unclear whether the effects are locally restricted to the high-energy-demanding retinal pigment epithelium or are also systematically present. Therefore, we measured mtDNA copy number (mtDNA-CN) in peripheral blood using a qPCR approach in elderly participants with and without AMD from the AugUR study (n = 2,262).
We found significantly lower mtDNA-CN in the blood of participants with early (n = 453) and late (n = 170) AMD compared to AMD-free participants (n = 1630). In regression analyses, we found lower mtDNA-CN to be associated with late AMD when compared with AMD-free participants. Each reduction of mtDNA-CN by one standard deviation increased the risk for late AMD by 24%. This association was most pronounced in geographic atrophy (odds ratio = 1.76), which has limited treatment options. These findings provide new insights into the relationship between mtDNA-CN in blood and AMD, suggesting that it may serve as a more accessible biomarker than mtDNA-CN in the retina.