Abstract
One of the most prominent age-related changes of retinal pigment epithelium (RPE) is the accumulation of melanolipofuscin granules, which could contribute to oxidative stress in the retina. The purpose of this study was to determine the ability of melanolipofuscin granules from younger and older donors to photogenerate reactive oxygen species, and to examine if natural antioxidants could modify the phototoxic potential of this age pigment. Electron paramagnetic resonance (EPR) oximetry, EPR-spin trapping, and time-resolved detection of near-infrared phosphorescence were employed for measuring photogeneration of superoxide anion and singlet oxygen by melanolipofuscin isolated from younger and older human donors. Phototoxicity mediated by internalized melanolipofuscin granules with and without supplementation with zeaxanthin and α-tocopherol was analyzed in ARPE-19 cells by determining cell survival, oxidation of cellular proteins, organization of the cell cytoskeleton, and the cell specific phagocytic activity. Supplementation with antioxidants reduced aerobic photoreactivity and phototoxicity of melanolipofuscin granules. The effect was particularly noticeable for melanolipofuscin mediated inhibition of the cell phagocytic activity. Antioxidants decreased the extent of melanolipofuscin-dependent oxidation of cellular proteins and disruption of the cell cytoskeleton. Although melanolipofuscin might be involved in chronic phototoxicity of the aging RPE, natural antioxidants could partially ameliorate these harmful effects.
Highlights
Retinal pigment epithelium (RPE) is the outermost part of the eye retina consisting of a single layer of cells adjacent to photoreceptors cells
The main aim of this study was to determine the photoreactivity and phototoxicity of melanolipofuscin isolated from retinal pigment epithelium (RPE) of human donors of different age, and to examine whether natural antioxidants could modulate the ability of the age pigment to photogenerate reactive oxygen species and disturb specific phagocytosis of RPE cells, their most important biological function
The results demonstrate that melanolipofuscin granules after phagocytosis by ARPE-19 cells were able to photoinduce oxidation of cellular proteins
Summary
Retinal pigment epithelium (RPE) is the outermost part of the eye retina consisting of a single layer of cells adjacent to photoreceptors cells. RPE of a normal human eye contains melanin granules, viewed as a photoprotective pigment and natural antioxidant [5,6]. Oxidative stress has been postulated to play an important role in neurodegenerative diseases, such as age-related macular degeneration (AMD) which is the predominant cause of blindness in people over 65 in developed Western countries [10]. Melanolipofuscin, rather than lipofuscin, might be the key age pigment of the human RPE responsible for photochemical reactions mediating chronic oxidative stress in the retina, which could lead to degenerative processes
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