8-hydroxy-2--deoxyguanosine and Retinitis-Pigmentosa

An imbalance between the production of reactive oxygen species (ROS) and anti-oxidant capacity results in oxidative injury to cellular components and molecules, which in turn disturbs the homeostasis of cells and organs. Although retinitis pigmentosa (RP) is a hereditary disease, non-genetic biological factors including oxidative stress also modulate or contribute to the disease progression. In animal models of RP, the degenerating retina exhibits marked oxidative damage in the nucleic acids, proteins, and lipids, and anti-oxidant treatments substantially suppress photoreceptor cell death and microgliosis. Although the mechanisms by which oxidative stress mediates retinal degeneration have not been fully elucidated, our group has shown that oxidative DNA damage and its defense system are key regulators of microglial activation and photoreceptor degeneration in RP. In this review, we summarize the current evidence regarding oxidative stress in animal models and patients with RP. The clinical efficacy of anti-oxidant treatments for RP has not been fully established. Nevertheless, elucidating key biological processes that underlie oxidative damage in RP will be pivotal to understanding the pathology and developing a potent anti-oxidant strategy that targets specific cell types or molecules under oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Catalase; Disease Models, Animal; DNA Damage; DNA Glycosylases; DNA Repair Enzymes; Gene Expression Regulation; Glutathione Peroxidase; Humans; Macular Degeneration; Microglia; Oxidative Stress; Phosphoric Monoester Hydrolases; Reactive Oxygen Species; Retina; Retinitis Pigmentosa; Superoxide Dismutase

Dietary carotenoids exhibit various biological activities, including antioxidative activity. In particular, astaxanthin, a type of carotenoid, is well known as a powerful antioxidant. We investigated whether astaxanthin would protect against light-induced retinal damage. In an in vivo study, ddY male mice were exposed to white light at 8,000 lux for 3 h to induce retinal damage. Five days after light exposure, retinal damage was evaluated by measuring electroretinogram (ERG) amplitude and outer nuclear layer (ONL) thickness. Furthermore, expression of apoptotic cells, 8-hydroxy-deoxyguanosine (8-OHdG), was measured. In an in vitro study, retinal damage was induced by white light exposure at 2,500 lux for 24 h, and propidium iodide (PI)-positive cells was measured and intracellular reactive oxygen species (ROS) activity was examined. Astaxanthin at 100 mg/kg inhibited the retinal dysfunction in terms of ERG and ONL loss and reduced the expression of apoptotic and 8-OHdG-positive cells induced by light exposure. Furthermore, astaxanthin protected against increases of PI-positive cells and intracellular reactive oxygen species (ROS) activity in 661W cells. These findings suggest that astaxanthin has protective effects against light-induced retinal damage via the mechanism of its antioxidative effect.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Ophthalmic; Animals; Antioxidants; Apoptosis; Cells, Cultured; Deoxyguanosine; Disease Models, Animal; Electroretinography; Light; Macular Degeneration; Male; Mice; Mice, Inbred Strains; Propidium; Reactive Oxygen Species; Retina; Retinal Cone Photoreceptor Cells; Retinitis Pigmentosa; Xanthophylls