Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of diseases in which one of a wide variety of mutations selectively causes rod photoreceptor cell death. After rods die, cone photoreceptors gradually die resulting in blindness. Antioxidants reduce cone cell death in rd1/rd1 mice indicating that cones die from oxidative damage in that model of rapidly progressive RP. In this study, we sought to determine if this observation could be generalized to models of other types of RP, rd10/rd10 mice, a model of more slowly progressive recessive RP, and Q344ter mice, a model of rapidly progressive dominant RP. Compared to appropriate vehicle-treated controls, rd10/rd10 and Q344ter mice treated between P18 and P35 with a mixture of antioxidants previously found to be effective in rd1/rd1 mice showed significantly greater cone survival. Antioxidant-treated rd10/rd10 mice showed preservation of cone function as shown by a significant increase in photopic ERG b-wave amplitudes, and surprisingly showed temporary preservation of scotopic a-wave amplitudes, prolonged rod survival, and slowed depletion of rhodopsin mRNA. These data suggest that oxidative damage contributes to cone cell death regardless of the disease causing mutation that leads to the demise of rods, and that in more slowly progressive rod degenerations, oxidative damage may also contribute to rod cell death. Protection from oxidative damage may be a broadly applicable treatment strategy in RP.

Komeima K ，Rogers BS ，Campochiaro PA 《-》

Antioxidants reduce cone cell death in a model of retinitis pigmentosa.

Komeima K ，Rogers BS ，Lu L ，Campochiaro PA ... -  《-》

N-Acetylcysteine promotes long-term survival of cones in a model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a major source of blindness caused by a large variety of mutations that lead to the death of rod photoreceptors. After rods die, cones gradually die from progressive oxidative damage. Several types of antioxidant formulations have been shown to reduce cone cell death over a relatively short-time frame, but in order for this strategy to be translated into a new treatment for patients with RP, prolonged effects will be needed. In this study, we determined that orally administered N-acetylcysteine (NAC) reduced cone cell death and preserved cone function by reducing oxidative damage in two models of RP, rd1(+/+) and rd10(+/+) mice. In rd10(+/+) mice, supplementation of drinking water with NAC promoted partial maintenance of cone structure and function for at least 6 months. Topical application of NAC to the cornea also reduced superoxide radicals in the retina and promoted survival and functioning of cones. Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, it is reasonable to consider clinical trials to evaluate the effects of prolonged treatment with NAC in patients with RP.

Lee SY ，Usui S ，Zafar AB ，Oveson BC ，Jo YJ ，Lu L ，Masoudi S ，Campochiaro PA ... -  《-》

Long-term preservation of cone photoreceptors and visual acuity in rd10 mutant mice exposed to continuous environmental enrichment.

Barone I ，Novelli E ，Strettoi E 《MOLECULAR VISION》

Different effects of valproic acid on photoreceptor loss in Rd1 and Rd10 retinal degeneration mice.

Mitton KP ，Guzman AE ，Deshpande M ，Byrd D ，DeLooff C ，Mkoyan K ，Zlojutro P ，Wallace A ，Metcalf B ，Laux K ，Sotzen J ，Tran T ... -  《MOLECULAR VISION》