Photoreceptor apoptosis control in animal models for retinitis pigmentosa by caspase inhibitor

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The effect of a caspase-3 inhibitor on photoreceptor apoptosis was investigated. Sixty mg/kg MNU was given intraperitoneally to 50 day old female Sprague-Dawley rats, and 4000 ng Ac-DEVD-CHO, a caspase-3 inhibitor, was injected intravitreally twice at 0 and 10 hr after MNU. In MNU-treated rats, the TUNEL index 24hr post-MNU was 79.5% in the peripheral and 83.7% in the central retina, while the Ac-DEVD-CHO injection significantly reduced it to 59.7% and 71.8%, respectively. Total retinal thickness 7 days after MNU was 38 μm in the peripheral and 75 μm in the central retina. Ac-DEVD-CHO injection increased these values to 72 and 77 μm, respectively. The retinal damage ratio 7 days after MNU was 98.5 %. Ac-DEVD-CHO injection significantly reduced this value to 54.4%, In C3H mice carrying the rd gene, 2 mg/kg of Ac-DEVD-CHO was injected intraperitoneally every other day from 8 days of age, and retinal damage was compared with that in saline-treated mice at 13 days and 17 days of age. At 13 days of age, total and outer retinal thickness in saline-treated mice was 140.3 μm and 37.5 μm, compared with 160.4 μm and 49.5 μm, respectively, in Ac-DEVD-CHO-treated mice (p<0.01, respectively)> However, at 17 days of age, Ac-DEVD-CHO treatment did not ameliorate retinal degeneration. In Both models, the caspase-3 inhibitor was partially effective in suppressing retinal degeneration through inhibition of the apoptosis of photoreceptor cells.