N-methyl-D-aspartate (NMDA) induced apoptosis in adult rabbit retinas

Previously we showed that apoptosis is involved in N-methyl-D-aspartate (NM DA) induced excitotoxicity in adult rat retinas. Since rabbits have a highe r endogenous level of glutamate in the retina and very different retinal st ructures, it is not clear if apoptosis is similarly involved in adult rabbi t retinas after intravitreal injection of NMDA. In this study, we used ultr astructural features, TdT-mediated biotin-dUTP nick end labeling (TUNEL) an d two caspase inhibitors to examine whether apoptosis is involved in NMDA-i nduced excitotoxicity in adult rabbit retinas. At 18 hr after an intravitre al injection of 400 nmoles NMDA, typical apoptotic features in degenerative cells in the retinal ganglion cen layer (RGCL) and the inner nuclear layer (INL) were noted by electron microscopy. TUNEL positive nuclei were detect ed in these layers as early as 4 hr showing maximal numbers at 18 hr. At 7 days, significant loss of nuclei from the RGCL was noted at the visual stre ak, the superior and the inferior retinas. These losses were abolished by s imultaneous administration of MK-801 and ameliorated by YVAD, a caspase-1 i nhibitor, but not by IETD, a caspase-8 inhibitor. These results indicated t hat, similar to adult rat retinas, apoptosis is involved in NMDA receptor-m ediated excitotoxicity in rabbit retinas and that specific caspases may pla y important roles. (C) 2000 Academic Press.