Involvement of NMDA-receptor in kainate-induced neurotoxicity in cultured fetal retinal neurons

Background: Both in vivo and in vitro studies suggest that excess stimulati on of non-NMDA receptors can result in massive neuronal death in the retina . In particular, murine amacrine neurons have been known to show marked sus ceptibility to the toxic effects of kainate. Purpose This study was designe d to examine and characterize the role of N-methyl-D-aspartate (NMDA) recep tor vs non-NMDA receptor in glutamate-induced neurotoxicity in the retina. methods: Primary cultures obtained from fetal rat retina (gestation day 16- 19) were used for the experiment. The neurotoxicity was assessed quantitati vely using the trypan blue exclusion method. Electrophysiological studies u sing patch-clamp techniques were performed to record whole-cell currents ev oked by these excitatory amino acids. Results: Removal of extracellular Ca2 + from the medium or application of MK-801 reduced the extent of cell death induced by the brief exposure to glutamate, NMDA, and kainate. By contrast , cell death induced by a 60-min exposure to kainate was not affected by MK -801. The electrophysiological study demonstrated that MK-801 abolished the whole-cell currents evoked by NMDA but had no effect on those induced by k ainate or AMPA. Conclusion: These findings demonstrate that brief exposure to kainate induces cell death by way of activating NMDA receptors in cultur ed fetal retinal neurons and that NMDA receptors are the predominant route of fetal retinal neurotoxicity induced by brief glutamate exposure.