Koller, Adriana and Lamina, Claudia and Brandl, Caroline and Zimmermann, Martina E. and Stark, Klaus J. and Weissensteiner, Hansi and Wuerzner, Reinhard and Heid, Iris M. and Kronenberg, Florian and Stewart, Jay (2023) Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (22): 16406. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
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 with plasmid normalization in elderly participants with and without AMD from the AugUR study (n = 2262). 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 (OR = 1.76, 95% CI 1.19-2.60, p = 0.004), 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OXIDATIVE STRESS; DNA HAPLOGROUPS; ASSOCIATION; CLASSIFICATION; RANIBIZUMAB; DAMAGE; RISK; CELL; mitochondrial DNA copy number; mtDNA abundance; age-related macular degeneration; aging; geographic atrophy |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2024 10:53 |
| Last Modified: | 12 Mar 2024 10:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59727 |
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