Glutamate-induced excitotoxicity in retina: neuroprotection with receptor antagonist, dextromethorphan, but not with calcium channel blockers.
The purpose of our studies was to evaluate different strategies for possible neuroprotection in glutamate-induced neurotoxicity in the retina. In a first set of experiments we attempted to determine if dextrorphan antagonism of glutamate action on NMDA receptors would protect against excitotoxic injury associated with secondary damage seen after surgical laser treatment in retina. In a second set of experiments, the effects of different calcium channel blockers in an in-vitro model of N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell excitotoxicity that utilized rabbit retinal explants were evaluated. Dextrorphan infusion prior to laser treatment of rabbit retina produced a significant decrease in the area of neural retinal damage. We attribute the apparent dextrorphan protection to attenuation of glutamate mediated excitotoxicity secondary to laser induced cell death. Preincubation of rabbit retinal explants with verapamil, nimodipine or omega-conotoxin MVIIA did not cause a significant change in NMDA induced cell death in the ganglion cell layer.
Calzada
Jorge I
JI
Department of Ophthalmology, The University of Tennessee Health Science Center, Memphis 38163, USA.
Jones
B Eric
BE
Netland
Peter A
PA
Johnson
Dianna A
DA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D003915:Dextromethorphan / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects / Q000494:pharmacology*; D017075:Laser Coagulation; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism*; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D003915:Dextromethorphan; D014700:Verapamil