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

Caspase抑制剂控制视网膜色素变性动物模型中的光感受器凋亡

• 批准号: 12671728
• 负责人: TSUBURA Airo
• 金额: $ 1.98万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671728/
• 关键词: Retinitis pigmentosa; N-methy1-N-nitrosourea; Apoptosis; Photoreceptor cell; Retinal degeneration; rd gene; Caspase; Caspase inhibitor; Bcl-2

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.

研究了半胱天冬酶-3抑制剂对感光细胞凋亡的影响。给50日龄雌性Sprague-Dawley大鼠腹腔注射60 mg/kg MNU，并在MNU后0和10 h玻璃体内注射4000 ng Ac-DEVD-CHO（半胱天冬酶-3抑制剂）两次。在MNU处理的大鼠中，MNU后24小时的TUNEL指数在周边视网膜中为79.5%，在中央视网膜中为83.7%，而Ac-DEVD-CHO注射分别将其显著降低至59.7%和71.8%。MNU后7天视网膜总厚度周边部为38 μm，中央部为75 μm。Ac-DEVD-CHO进样使这些值分别增加至72和77 μm。MNU后7天视网膜损伤率为98.5%。Ac-DEVD-CHO注射使该值显著降低至54.4%。在携带rd基因的C3 H小鼠中，从8日龄起每隔一天腹腔内注射2 mg/kg Ac-DEVD-CHO，并在13日龄和17日龄时与盐水处理的小鼠的视网膜损伤进行比较。在13日龄时，盐水处理的小鼠的总视网膜厚度和外视网膜厚度分别为140.3 μm和37.5 μm，而Ac-DEVD-CHO处理的小鼠分别为160.4 μm和49.5 μm（分别为p<0.01）。然而，在17日龄时，Ac-DEVD-CHO处理没有改善视网膜变性。在这两种模型中，半胱天冬酶-3抑制剂通过抑制感光细胞的凋亡在抑制视网膜变性方面部分有效。

项目成果

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