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Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood

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 c...

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Autores principales: Koller, Adriana, Lamina, Claudia, Brandl, Caroline, Zimmermann, Martina E., Stark, Klaus J., Weissensteiner, Hansi, Würzner, Reinhard, Heid, Iris M., Kronenberg, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671207/
https://www.ncbi.nlm.nih.gov/pubmed/38003595
http://dx.doi.org/10.3390/ijms242216406
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author Koller, Adriana
Lamina, Claudia
Brandl, Caroline
Zimmermann, Martina E.
Stark, Klaus J.
Weissensteiner, Hansi
Würzner, Reinhard
Heid, Iris M.
Kronenberg, Florian
author_facet Koller, Adriana
Lamina, Claudia
Brandl, Caroline
Zimmermann, Martina E.
Stark, Klaus J.
Weissensteiner, Hansi
Würzner, Reinhard
Heid, Iris M.
Kronenberg, Florian
author_sort Koller, Adriana
collection PubMed
description 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.
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spelling pubmed-106712072023-11-16 Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood Koller, Adriana Lamina, Claudia Brandl, Caroline Zimmermann, Martina E. Stark, Klaus J. Weissensteiner, Hansi Würzner, Reinhard Heid, Iris M. Kronenberg, Florian Int J Mol Sci Article 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. MDPI 2023-11-16 /pmc/articles/PMC10671207/ /pubmed/38003595 http://dx.doi.org/10.3390/ijms242216406 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koller, Adriana
Lamina, Claudia
Brandl, Caroline
Zimmermann, Martina E.
Stark, Klaus J.
Weissensteiner, Hansi
Würzner, Reinhard
Heid, Iris M.
Kronenberg, Florian
Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood
title Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood
title_full Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood
title_fullStr Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood
title_full_unstemmed Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood
title_short Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood
title_sort systemic evidence for mitochondrial dysfunction in age-related macular degeneration as revealed by mtdna copy number measurements in peripheral blood
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671207/
https://www.ncbi.nlm.nih.gov/pubmed/38003595
http://dx.doi.org/10.3390/ijms242216406
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