Interleukin-1β Converting Enzyme (ICE) like activities in apoptosis of retinal neurons after retinal ischemia-reperfusion injury

Purpose. To examine the role of interleukin-1β converting enzyme (ICE) like activities in apoptosis of inner retinal neurons. Methods. Retinal ischemia was induced in albino Lewis rats through the insertion of a cannula into the anterior chamber connected to a saline column. Intraocular pressure was kept at 110 mm Hg for 60 min. with elevated saline column. An ICE inhibitor, Ac-Tyr-Val-Ala-Asp-CMK (YVAD.CMK), at 100 μM in 0.1 M phosphate buffered saline (PBS), pH 7.4, or 0.1 M PBS for control was infused into the anterior chamber during ischemia (IVOS 35:3163-3168, 1994). Rats were killed at 18 hr after the insult to measure the apoptotic response by examining intranucleosomal fragmentation of retinal DNA with agarose gel electrophoresis or at 7 days to measure the tissue response by morphometry of the inner retinal thickness (IRT). Immunoreactivity (IM) of ICE like enzymes after the insult was followed with antibodies to CPP32 and ICH-1_L. Results. YVAD.CMK inhibited the expression of the ladder pattern in DNA fragmentation study and protected the retina as measured by morphometry of IRT at 7 day. IM of CPP32 and ICH-1_L. increased in the ganglion cell and inner nuclear layers at 8-18 hours after reperfusion. Conclusion. These findings are consistent with the hypothesis that ICE like enzymes may play an important role in apoptosis of inner retinal neurons.