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Katsuaki Miki, Akiko Miki, Shinichi Usui, Peter A campochiaro; Combination Antioxidant Therapy for Retinitis Pigmentosa (RP). Invest. Ophthalmol. Vis. Sci. 2011;52(14):4979.
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© ARVO (1962-2015); The Authors (2016-present)
To identify an optimal antioxidant regimen for treatment of RP.
Rd10+/+ mice were given drinking water supplemented with 5mg/ml dextromethorphan (DM, an NADPH oxidase inhibitor), 2.5 mg/ml phenyl-n-tert-butylnitrone (PBN), 7 mg/ml N-acetylcysteine (NAC), or all three between postnatal day (P) 21 and P50. Retinal function was assessed by electroretinograms (ERGs), rod survival was assessed by measurement of outer nuclear layer (ONL) thickness at P35, and cone survival was determined by measuring cone cell density in peanut agglutinin-stained retinal whole mounts at P50. Oxidative damage was assessed by ELISA for carbonyl adducts on proteins at P35.
At P50, mean (±SEM) photopic ERG b-wave amplitudes (µV) were significantly greater in rd10+/+ mice treated with DM (16.6±1.3, p<0.05), PBN (17.9±2.0, p<0.05), NAC (21.2±1.3, p<0.05), or DM+PBN+NAC (38.1±1.3, p<0.01) compared to untreated rd10+/+ mice (11.3±1.2). Mean cone density (cones/0.0529mm2) was also increased in rd10+/+ mice treated with DM (72±2, p<0.05), PBN (73±2, p<0.05), NAC (128±3, p<0.05), or DM+PBN+NAC (140±4, p<0.01) compared to untreated rd10+/+ mice (58±2). Each of the regimens reduced carbonyl adducts an indicator of oxidative damage.
DM, PBN, and NAC provide additive benefit for maintenance of cone function and survival in a model of RP supporting consideration of this regimen for clinical trials.
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