Caspase-3 inhibitor rescues N-methyl-N-nitrosourea-induced retinal degeneration in Sprague-Dawley rats

The effect of a caspase-3 inhibitor on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration was investigated. Sixty mg kg(-1) MNU was given intra peritoneally 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 h r after MNU. In both peripheral and central retina, an apoptotic index of t he photoreceptor cells 24 hr after MNU treatment was calculated by TUNEL la beling, and retinal damage 7 days after MNU treatment was evaluated from re tinal thickness and a retinal damage ratio (length of damaged retina:whole retinal length). In MNU-treated rats, the TUNEL index 24 hr post-MNU was 79 .5% in the peripheral and 83.7% in the central retina, while the Ac-DEVD-CH O injection significantly reduced it to 59.7 and 71.8%, respectively. Total retinal thickness 7 days after MNU was 38 mum in the peripheral and 75 mum in the central retina. Ac-DEVD-CHO injection increased these values to 72 and 77 mum, respectively. The retinal damage ratio 7 days after MNU was 98. 5%. Ac-DEVD-CHO injection significantly reduced this value to 54.4%. The us e of a caspase-3 inhibitor was effective in the suppression of MNU-induced retinal apoptosis and may be a therapeutic intervention in human retinitis pigmentosa. (C) 2000 Academic Press.