title: DNA damage response and autophagy in the degeneration of retinal pigment epithelial cells-Implications for age-related macular degeneration (AMD).
abstract: In this review we will discuss the links between autophagy, a mechanism involved in the maintenance of cellular homeostasis and controlling cellular waste management, and the DNA damage response (DDR), comprising various mechanisms preserving the integrity and stability of the genome. A reduced autophagy capacity in retinal pigment epithelium has been shown to be connected in the pathogenesis of age-related macular degeneration (AMD), an eye disease. This degenerative disease is a major and increasing cause of vision loss in the elderly in developed countries, primarily due to the profound accumulation of intra- and extracellular waste: lipofuscin and drusen. An abundance of reactive oxygen species is produced in the retina since this tissue has a high oxygen demand and contains mitochondria-rich cells. The retina is exposed to light and it also houses many photoactive molecules. These factors are clearly reflected in both the autophagy and DNA damage rates, and in both nuclear and mitochondrial genomes. It remains to be revealed whether DNA damage and DDR capacity have a more direct role in the development of AMD.
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland. Electronic address: Juha.Hyttinen@uef.fi.
authors.forename: Juha M T
authors.initials: JMT
authors.lastname: Hyttinen
authors.affiliation: Department of Molecular Genetics, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Błasiak
authors.affiliation: Institute of Biotechnology, Developmental Biology Program, University of Helsinki, P.O. Box 56, FI-00014, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Niittykoski
authors.affiliation: Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, FI-70029, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Kinnunen
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, FI-70029, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D012168:Retinal Pigments / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008062:Lipofuscin; D017382:Reactive Oxygen Species; D012168:Retinal Pigments
keywords: Age related macular degeneration; Autophagy; DNA damage response; Reactive oxygen species; Retinal pigment epithelium