Effect of inhibitors of Interleukin-1β Converting Enzyme (ICE), poly(ADP-ribose) polyermase (PAP) and Nitric Oxide Synthase (NOS) on light-induced apoptosis of photoreceptors

Purpose. To explore the pathway(s) of apoptosis in light-induced photoreceptor cell death. Methods. Thirty day old albino Lewis rats were kept at 12 hour dark and 12 hour light cycles for 14 days, dark adapted for 24 hrs. and exposed to 300-320 ft-c of green light (480-520 nm) for 12 hours (IOVS 35:1517, 1994). Two μl of 100 μM of Ac-Tyr-Val-Ala-Asp.CMK (YVAD), 10 mM 3-amino-benzylamide(3-ABA), 1 mM N-nitro-arginine (NNA), inhibitors of ICE, PAP and NNA respectively, or 0.1M PBS (vehicle), pH 7.4, was given intravitreally and immediately after light exposure. Animals were killed at 24 hours after light exposure, a time when the characteristic ladder pattern of DNA fragmentation of retinal DNA was most evident on agarose gel electrophoresis. Retinal DNA was collected and analyzed by agarose gel electrophoresis. Results. When compared to the control, both 3-ABA and NNA but not YVAD treatments inhibited the expression of ladder pattern in the fragmentation of retinal DNA after light exposure. Conclusion These observations suggested that PAP and NOS may be involved in light-induced apoptosis of photoreceptors. The involvement of ICE and the specific roles of PAP and NOS remains to be further elucidated.