High vulnerability of GABA-immunoreactive neurons to kainate in rat retinal cultures: correlation with the kainate-stimulated cobalt uptake.
Like other areas of the central nervous system, the retina is highly vulnerable to ischemia. In particular, neurons in the inner nuclear layer, including gamma-amino butyric acid (GABA)-ergic amacrine neurons, are highly vulnerable. Since excitotoxicity is likely a major mechanism of ischemic retinal injury, using rat retinal cell culture, we examined whether GABAergic retinal neurons are differentially vulnerable to particular excitotoxins. The neuronal population as a whole, identified by anti-microtubule associated protein-2 (MAP-2) immunocytochemistry, was equally vulnerable to kainate, but more resistant to N-methyl-d-aspartate (NMDA) than cultured cortical neurons. Compared to Thy-1 immunoreactive neurons, GABA immunoreactive neurons were more vulnerable to kainate, but more resistant to NMDA neurotoxicity. Double staining of cultures with anti-GABA immunocytochemistry and the kainate-stimulated cobalt uptake method, revealed a close correlation between the two. However, unlike in other neuronal cells, there was no clear correlation between GluR2 immunoreactivity and the cobalt staining. The heightened vulnerability of GABAergic neurons to kainate, as compared to the general neuronal population, may be due to the calcium-permeable AMPA/kainate receptors they have, as identified functionally by the kainate-stimulated cobalt uptake staining. Since these neurons are preferentially injured in ischemia, AMPA/kainate receptor-mediated neurotoxicity may contribute significantly to ischemic retinal injury.
Yoon
Y H
YH
Department of Ophthalmology, University of Ulsan, College of Medicine, 388-1 Poongnap-Dong Songpa-Gu, Seoul 138-040, South Korea.
Jeong
K H
KH
Shim
M J
MJ
Koh
J Y
JY
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000493:pharmacokinetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D003035:Cobalt; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D007608:Kainic Acid