N-methyl-D-aspartate-induced excitotoxicity in adult rat retina is antagonized by single systemic injection of MK-801

Intravitreal injection of N-methyl-D-aspartate (NMDA) produced a substantia l damage to the adult rat retina that was largely restricted to inner retin al layers, including the ganglion cell layer (GCL), inner nuclear layer (IN L), inner, and outer plexiform layers. This retinal damage was significantl y reduced by a systemic injection of a low dose of MK-801 (0.5 mg/kg), a po tent NMDA-receptor antagonist. This neuroprotection was dose dependent and was most effective when the antagonist was given 1 h before NMDA insult. An intraperitoneal injection of 0.5 mg/kg MK-801 provided a virtually complet e protection to the retina to the NMDA-induced toxicity, as indicated quant itatively by the number of DiI-filled retinal ganglion cells, the number of cells in the GCL and INL that undergo DNA fragmentation, and the edematous changes in retinal thickness. A post-lesion administration of MK-801 was s till able to provide an effective neuroprotective effect to the retina, but this protection was lost when MK-801 was given 4 h after NMDA exposure. Th e current results indicate a therapeutic potential of systemic application of MK-801 in protecting the adult rat retina From neurologic disorders rela ted to excessive activation of NMDA receptors.