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Lipofuscin-formation in cultured retinal pigment epithelial cells is related to their melanin content
Authors:Sundelin S P  Nilsson S E  Brunk U T
Institution:1. Divisions of Division of Ophthalmology, Department of Neuroscience and Locomotion, Linköping University, Linköping, Sweden and Division of;2. Pathology II, Department of Neuroscience and Locomotion, Linköping University, Linköping, Sweden;2. Department of Ophthalmology, Faculty of Medicine, Pamukkale University, Denizli, Turkey;4. Vision Sciences and Human Biofactors Laboratory, Behavioral and Brain Sciences Program, Department of Psychology, The University of Georgia, Athens, GA;1. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China;2. Beijing Anzhen Hospital, Capital Medical University, Beijing, China;1. Institut de la Màcula; Barcelona, Spain;2. Barcelona Macula Foundation; Barcelona, Spain;3. Inserm, Bordeaux Population Health Research Center, Université de Bordeaux, Bordeaux, France;4. The Wellcome-Wolfson Institute for Experimental Medicine, Queens University Belfast, Belfast, United Kingdom
Abstract:Age-related macular degeneration (AMD), the leading cause of blindness in the developed world, is accompanied by degeneration of the retinal pigment epithelial (RPE) cells. There is an inverse correlation between the melanin content of the eye and the incidence of AMD. Lipofuscin (LF)-accumulation in RPE cells accompanies the process of aging, and may also be related to AMD. This study was designed to evaluate the effect of melanin/melanosomes on the rate of LF formation in cultured rabbit and bovine RPE cells subjected to oxidative stress (40% normobaric O(2)) and daily supplementation with photoreceptor outer segments for 4 weeks. The LF content was measured at 0, 2, and 4 weeks in RPE cells from pigmented and albino rabbits, as well as in pigment-rich and pigment-poor bovine cells. Albino rabbit and pigment-poor bovine cells accumulated significantly higher amounts of LF than pigmented rabbit cells and pigment-rich bovine RPE cells after both 2 and 4 weeks of exposure. Autometallography of melanin-containing cells, without previous exposure to ammonium sulfide, showed a positive outcome, indicating either the occurrence of pre-existing iron-sulphur clusters or an extremely high intrinsic reducing capacity. These results suggest that melanin acts as an efficient antioxidant, perhaps by interacting with transition metals.
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