Antioxidants reduce cone cell death in a model of retinitis pigmentosa

In a study involving a rd1 mouse model of retinitis pigmentosa (RP) – a group of diseases which involve damage to the retina, and are caused by a large number of mutations that result in rod photoreceptor cell death, which is followed by a gradual death of cones, the mechanism of which is unknown, characterized by decreased or loss of night vision, peripheral vision, and in advanced stages, central vision – daily injections with various antioxidant supplements (vitamin E, vitamin C, and alpha-lipoic acid) was found to reduce oxidative damage in cones, increase cone cell density, increase medium-wavelength cone opsin mRNA, and preserve some cone function. In this mouse model, by day 18, rods were completely degenerated, and by day 35, 85% of cones were dead. Mice were first injected with a combination of antioxidants, which included alpha-tocopherol (200 mg/kg in olive oil), ascorbic acid (250 mg/kg in PBS), and alpha-lipoic acid (100 mg/kg in PBS/30% ethanol), along with a metalloporphyrin superoxide dismutase mimetic that protects against intracellular generation of reactive oxygen species, MnTBAP (10 mg/kg in PBS). When treated with this combination, some preservation of cone function was found, as determined by significantly greater mean b-wave amplitude found in mice treated with antioxidants, as compared to mice not treated with antioxidants. Furthermore, antioxidants were found to help preserve mRNA synthesis in the cell bodies of one population of cones, as suggested by the significantly greater m-cone opsin mRNA in the retinas of mice treated with antioxidants as compared to those who were not. When the researchers injected the antioxidants individually to determine specific effects of the different antioxidants, it was found that both alpha-tocopherol and alpha-lipoic acid promoted survival of cones after the rods had all died, with approximately 40% of cones surviving, as compared to the other groups. These results suggest that cone cell death which follows rod cell death may be linked to high levels of oxygen in the retina (oxidative damage), and therefore, antioxidant may have a role to play in delaying the progression of vision loss in persons with retinitis pigmentosa. The authors point out the dosages used in this study would not be recommended for humans. Additional research is needed.

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