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Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration.
Prog Retin Eye Res. 2020 Apr 13 [Online ahead of print]PR

Abstract

Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is considered to be a key factor in age-related macular degeneration (AMD) pathology. RPE cells are constantly exposed to oxidative stress that may lead to the accumulation of damaged cellular proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. The ubiquitin-proteasome and the lysosomal/autophagy pathways are the two major proteolytic systems to remove damaged proteins and organelles. There is increasing evidence that proteostasis is disturbed in RPE as evidenced by lysosomal lipofuscin and extracellular drusen accumulation in AMD. Nuclear factor-erythroid 2-related factor-2 (NFE2L2) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) are master transcription factors in the regulation of antioxidant enzymes, clearance systems, and biogenesis of mitochondria. The precise cause of RPE degeneration and the onset and progression of AMD are not fully understood. However, mitochondria dysfunction, increased reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) damage are observed together with increased protein aggregation and inflammation in AMD. In contrast, functional mitochondria prevent RPE cells damage and suppress inflammation. Here, we will discuss the role of mitochondria in RPE degeneration and AMD pathology focused on mtDNA damage and repair, autophagy/mitophagy signaling, and regulation of inflammation. Mitochondria are putative therapeutic targets to prevent or treat AMD.

Authors+Show Affiliations

Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland and Kuopio University Hospital, P.O. Box 1627, FI-70211, Kuopio, Finland. Electronic address: kai.kaarniranta@uef.fi.Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland and Tays Eye Centre, Tampere University Hospital, P.O.Box 2000, 33521 Tampere, Finland.Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236, Lodz, Poland.Department of Biomedicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.The Stephen J. Ryan Initiative for Macular Research (RIMR), Doheny Eye Institute, 1355 San Pablo St, Los Angeles, CA, 90033, USA.School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.Glia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, PA 15224, USA; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Room M035 Robert and Clarice Smith Bldg, 400 N Broadway, Baltimore, MD, 21287, USA.Department of Ophthalmology and Visual Neurosciences, 2001 6th St SE, University of Minnesota, Minneapolis, MN 55455, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32298788

Citation

Kaarniranta, Kai, et al. "Mechanisms of Mitochondrial Dysfunction and Their Impact On Age-related Macular Degeneration." Progress in Retinal and Eye Research, 2020, p. 100858.
Kaarniranta K, Uusitalo H, Blasiak J, et al. Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration. Prog Retin Eye Res. 2020.
Kaarniranta, K., Uusitalo, H., Blasiak, J., Felszeghy, S., Kannan, R., Kauppinen, A., Salminen, A., Sinha, D., & Ferrington, D. (2020). Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration. Progress in Retinal and Eye Research, 100858. https://doi.org/10.1016/j.preteyeres.2020.100858
Kaarniranta K, et al. Mechanisms of Mitochondrial Dysfunction and Their Impact On Age-related Macular Degeneration. Prog Retin Eye Res. 2020 Apr 13;100858. PubMed PMID: 32298788.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration. AU - Kaarniranta,Kai, AU - Uusitalo,Hannu, AU - Blasiak,Janusz, AU - Felszeghy,Szabolcs, AU - Kannan,Ram, AU - Kauppinen,Anu, AU - Salminen,Antero, AU - Sinha,Debasish, AU - Ferrington,Deborah, Y1 - 2020/04/13/ PY - 2019/10/25/received PY - 2020/03/18/revised PY - 2020/03/19/accepted PY - 2020/4/17/pubmed PY - 2020/4/17/medline PY - 2020/4/17/entrez KW - Age-related macular degeneration KW - Aggregation KW - Aging KW - Autophagy KW - Clearance KW - Degeneration KW - Mitochondria KW - Mitophagy KW - Retina KW - Retinal pigment epithelium SP - 100858 EP - 100858 JF - Progress in retinal and eye research JO - Prog Retin Eye Res N2 - Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is considered to be a key factor in age-related macular degeneration (AMD) pathology. RPE cells are constantly exposed to oxidative stress that may lead to the accumulation of damaged cellular proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. The ubiquitin-proteasome and the lysosomal/autophagy pathways are the two major proteolytic systems to remove damaged proteins and organelles. There is increasing evidence that proteostasis is disturbed in RPE as evidenced by lysosomal lipofuscin and extracellular drusen accumulation in AMD. Nuclear factor-erythroid 2-related factor-2 (NFE2L2) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) are master transcription factors in the regulation of antioxidant enzymes, clearance systems, and biogenesis of mitochondria. The precise cause of RPE degeneration and the onset and progression of AMD are not fully understood. However, mitochondria dysfunction, increased reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) damage are observed together with increased protein aggregation and inflammation in AMD. In contrast, functional mitochondria prevent RPE cells damage and suppress inflammation. Here, we will discuss the role of mitochondria in RPE degeneration and AMD pathology focused on mtDNA damage and repair, autophagy/mitophagy signaling, and regulation of inflammation. Mitochondria are putative therapeutic targets to prevent or treat AMD. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/32298788/Mechanisms_of_mitochondrial_dysfunction_and_their_impact_on_age-related_macular_degeneration L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(20)30030-6 DB - PRIME DP - Unbound Medicine ER -
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