| Co-Investigator(Kenkyū-buntansha) |
HAGA Satomi Nara Med.Univ., Faculty of Medicine, Assistant Professor, 医学部, 講師 (20192263)
MIKI Hirohiko Kansai Med.Univ., Faculty of Medicine, Associate Professor, 医学部, 助教授 (30077771)
SHIKATA Nobuaki Kansai Med.Univ., Faculty of Medicine, Associate Professor, 医学部, 助教授 (00121939)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
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.
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