Involvement of NMDA-receptor in kainate-induced neurotoxicity in cultured fetal retinal neurons.
BACKGROUND
Both in vivo and in vitro studies suggest that excess stimulation of non-NMDA receptors can result in massive neuronal death in the retina. In particular, murine amacrine neurons have been known to show marked susceptibility to the toxic effects of kainate.


OBJECTIVE
This study was designed to examine and characterize the role of N-methyl-D-aspartate (NMDA) receptor 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 quantitatively using the trypan blue exclusion method. Electrophysiological studies using patch-clamp techniques were performed to record whole-cell currents evoked 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 kainate or AMPA.


CONCLUSIONS
These findings demonstrate that brief exposure to kainate induces cell death by way of activating NMDA receptors in cultured fetal retinal neurons and that NMDA receptors are the predominant route of fetal retinal neurotoxicity induced by brief glutamate exposure.
Zhang
S
S
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Japan.
Kashii
S
S
Yasuyoshi
H
H
Honda
Y
Y
Ujihara
H
H
Sasa
M
M
Tamura
Y
Y
Akaike
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity; D007608:Kainic Acid / Q000633:toxicity*; D008564:Membrane Potentials; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012160:Retina / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; D002118:Calcium