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

研究caspase-3抑制剂对光感受器细胞凋亡的影响。给50日龄雌性SD大鼠腹腔注射MNU 60 mg/kg，并于MNU后0和10h玻璃体腔内注射caspase-3抑制剂Ac-DEVD-CHO 4000 ng。在MNU处理的大鼠，MNU后24小时外周和中央视网膜的TUNEL指数分别为79.5%和83.7%，而Ac-DEVD-CHO注射后分别显著降低到59.7%和71.8%。术后7d外周视网膜总厚度为38μm，中心视网膜为75μm。注射Ac-DEVDCHO使上述值分别增加到72和77μm。MNU后7d视网膜损伤率为98.5%。Ac-DEVD-CHO注射使Rd基因携带者的视网膜损伤降低到54.4%，从8日龄起隔日给C3H小鼠注射Ac-DEVD-CHO 2 mg/kg，并在第13天和第17天与生理盐水对照组比较。13日龄时，生理盐水处理组小鼠视网膜总厚度和外壁厚度分别为140.3μm和37.5μm，而Ac-DEVD-CHO组分别为160.4μm和49.5μm。然而，17日龄时，Ac-DEVD-CHO处理组小鼠视网膜变性并未得到改善。在两种模型中，caspase-3抑制剂通过抑制光感受器细胞的凋亡而部分有效地抑制视网膜变性。

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.