PGC-1α protects RPE cells of the aging retina against oxidative stress-induced degeneration through the regulation of senescence and mitochondrial quality control. The significance for AMD pathogenesis
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PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator of many genes involved in energy management and mitochondrial biogenesis. PGC-1α expression is associated with cellular senescence, organismal aging, and many age-related diseases, including AMD (age-related macular degeneration), an important global issue concerning vision loss. We and others have developed a model of AMD pathogenesis, in which stress-induced senescence of retinal pigment epithelium (RPE) cells leads to AMD-related pathological changes. PGC-1α can decrease oxidative stress, a key factor of AMD pathogenesis related to senescence, through upregulation of antioxidant enzymes and DNA damage response. PGC-1α is an important regulator of VEGF (vascular endothelial growth factor), which is targeted in the therapy of wet AMD, the most devastating form of AMD. Dysfunction of mitochondria induces cellular senescence associated with AMD pathogenesis. PGC-1α can improve mitochondrial biogenesis and negatively regulate senescence, although this function of PGC-1α in AMD needs further studies. Post-translational modifications of PGC-1α by AMPK (AMP kinase) and SIRT1 (sirtuin 1) are crucial for its activation and important in AMD pathogenesis.
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Mitochondrial dysfunction contributes to AMD.
“There have been a number of studies in the literature which show that mitochondrial dysfunction contributes to AMD (Fisher and Ferrington, 2018; Kaarniranta et al., 2018).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Kaarniranta et al., 2018
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Abdullahi, A., Olaleke, B., Adeyemi, R. O., & Oluwatosin, S. (2020) · Journal of Emerging Technologies and Innovative Research
- Authors
- Kaarniranta, K., Kajdanek, J., Morawiec, J., Pawlowska, E., & Blasiak, J.
- Affiliations
- University of Eastern Finland (FI)
- University of Łódź (PL)
- Medical University of Lodz (PL)
- Department of Orthodontics, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland
- Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2018-08-07
- Volume
- 19
- Issue
- 8
- Pages
- 2317
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC6121367
- OpenAlex
- W2885494745
- Cited by
- 112
- References
- 117
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 11 · 2023: 12 · 2022: 18 · 2021: 22 · 2020: 20 · 2019: 12 · 2012: 1
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Narodowym Centrum Nauki (2017/27/B/NZ3/00872)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- PGC-1α, retinal pigment epithelium, age-related macular degeneration, oxidative stress, cellular senescence, mitochondrial quality control, mitochondrial biogenesis, vascular endothelial growth factor, AMPK, SIRT1, post-translational modification, DNA damage response, antioxidant enzymes, neovascular age-related macular degeneration
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aging, Animals, Humans, Macular Degeneration, Mitochondria, Oxidative Stress, Retinal Pigment Epithelium
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