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 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 both peripheral and central retina, an apoptotic index of the photoreceptor cells 24 hr after MNU treatment was calculated by TUNEL labeling, and retinal damage 7 days after MNU treatment was evaluated from retinal 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-CHO injection significantly reduced it to 59.7 and 71.8%, respectively. Total retinal thickness 7 days after MNU was 38 microm in the peripheral and 75 microm in the central retina. Ac-DEVD-CHO injection increased these values to 72 and 77 microm, respectively. The retinal damage ratio 7 days after MNU was 98.5%. Ac-DEVD-CHO injection significantly reduced this value to 54.4%. The use 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.
Copyright 2000 Academic Press.