Caspase-3 Inhibitor Rescues N -Methyl- N -nitrosourea-induced Retinal Degeneration in Sprague–Dawley Rats

• Published in: Experimental eye research 2000-12, Vol.71 (6), p.629-635
• Main Authors: Yoshizawa, Katsuhiko, Yang, Jihong, Senzaki, Hideto, Uemura, Yoshiko, Kiyozuka, Yasuhiko, Shikata, Nobuaki, Oishi, Yuji, Miki, Hirohiko, Tsubura, Airo
• Format: Article
• Language: English
• Subjects: Ac-DEVD-CHO; Animals; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caspase Inhibitors; caspase-3 inhibitor; Caspases - pharmacology; Caspases - therapeutic use; Eye and associated structures. Visual pathways and centers. Vision; Female; Fundamental and applied biological sciences. Psychology; In Situ Nick-End Labeling; Methylnitrosourea - pharmacology; N -methyl- N -nitrosourea; photoreceptor cell; Photoreceptor Cells, Vertebrate - drug effects; Photoreceptor Cells, Vertebrate - pathology; rat; Rats; Rats, Sprague-Dawley; retinal degeneration; Retinal Degeneration - chemically induced; Retinal Degeneration - drug therapy; Vertebrates: nervous system and sense organs
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1006/exer.2000.0921

The effect of a caspase-3 inhibitor on N -methyl- N -nitrosourea (MNU)-induced retinal degeneration was investigated. Sixty mgkg−1MNU was given intraperitoneally to 50 day old female Sprague–Dawley rats, and 4000ng Ac-DEVD-CHO, a caspase-3 inhibitor, was injected intravitreally twice at 0 and 10hr after MNU. In both peripheral and central retina, an apoptotic index of the photoreceptor cells 24hr 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 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 38μ m in the peripheral and 75μ m in the central retina. Ac-DEVD-CHO injection increased these values to 72 and 77μ m, 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.