Antioxidants reduce cone cell death in a model of retinitis pigmentosa

K Komeima, BS Rogers, L Lu… - Proceedings of the …, 2006 - National Acad Sciences
K Komeima, BS Rogers, L Lu, PA Campochiaro
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
Retinitis pigmentosa (RP) is a label for a group of diseases caused by a large number of
mutations that result in rod photoreceptor cell death followed by gradual death of cones. The
mechanism of cone cell death is uncertain. Rods are a major source of oxygen utilization in
the retina and, after rods die, the level of oxygen in the outer retina is increased. In this study,
we used the rd1 mouse model of RP to test the hypothesis that cones die from oxidative
damage. A mixture of antioxidants was selected to try to maximize protection against …
Retinitis pigmentosa (RP) is a label for a group of diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cones. The mechanism of cone cell death is uncertain. Rods are a major source of oxygen utilization in the retina and, after rods die, the level of oxygen in the outer retina is increased. In this study, we used the rd1 mouse model of RP to test the hypothesis that cones die from oxidative damage. A mixture of antioxidants was selected to try to maximize protection against oxidative damage achievable by exogenous supplements; α-tocopherol (200 mg/kg), ascorbic acid (250 mg/kg), Mn(III)tetrakis (4-benzoic acid) porphyrin (10 mg/kg), and α-lipoic acid (100 mg/kg). Mice were treated with daily injections of the mixture or each component alone between postnatal day (P)18 and P35. Between P18 and P35, there was an increase in two biomarkers of oxidative damage, carbonyl adducts measured by ELISA and immunohistochemical staining for acrolein, in the retinas of rd1 mice. The staining for acrolein in remaining cones at P35 was eliminated in antioxidant-treated rd1 mice, confirming that the treatment markedly reduced oxidative damage in cones; this was accompanied by a 2-fold increase in cone cell density and a 50% increase in medium-wavelength cone opsin mRNA. Antioxidants also caused some preservation of cone function based upon photopic electroretinograms. These data support the hypothesis that gradual cone cell death after rod cell death in RP is due to oxidative damage, and that antioxidant therapy may provide benefit.
National Acad Sciences