Retinal neurones containing kainate receptors are influenced by exogenous kainate and ischaemia while neurones lacking these receptors are not -- melatonin counteracts the effects of ischaemia and kainate.
The present experiments were carried out on three types of neurone in primary rabbit retinal cultures. One cell-type, bipolar neurones, have glutamate APB-type metabotropic receptors and can be identified by the presence of thetaPKC-immunoreactivity. The other two cell-types are primarily amacrine cells and can be 'stained' for the localisation of GABA immunoreactivity or for serotonin taken up from the medium. Most of the serotonin-accumulating and GABA-containing neurones contain glutamate kainate-type receptors. Exposure of the cultures to treatment of kainate (50 microM) or experimental ischaemia (8 h followed by 16 h reoxygenation) produced essentially similar findings. The serotonin-accumulating and GABA cells were affected as they were drastically reduced in numbers while the numbers of thetaPKC-containing cells were unaffected. Inclusion of the kainate/AMPA antagonist CNQX (100 microM) or melatonin (100 microM) to the medium during kainate or ischaemia treatments largely prevented the detrimental influences on the serotonin-accumulating and GABA cells. It is concluded that during experimental ischaemia excessive glutamate is released to influence cells which contain kainate and APB-type receptors. However, only the neurones containing the kainate receptors are negatively affected with the generation of free radicals. Melatonin or CNQX protects against this effect by scavenging free radicals or acting at the receptor level, respectively.
Cazevieille
C
C
Nuffield Laboratory of Ophthalmology, University of Oxford, UK.
Osborne
N N
NN
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007511:Ischemia / Q000188:drug therapy*; D007608:Kainic Acid / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D011817:Rabbits; D018092:Kainic Acid Receptors / Q000187:drug effects*; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D012171:Retinal Vessels / Q000187:drug effects*
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D008550:Melatonin; D018092:Kainic Acid Receptors