The effects of
glutamate receptor agonists were evaluated, by utilizing the electron microscope, in a photothrombotic occlusion model of rat retinal vessels in order to study the ischemic damage and its antagonism in each morphologically identified population of retinal neurons. Rats were systemically injected with
rose bengal fluorescein dye and one of their eyes was then exposed to bright light. This treatment caused neuronal damage and reduced the activities of the neuronal marker
enzymes,
choline acetyltransferase and
glutamate decarboxylase, by approximately 75%. A single
intravitreal injection of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzoquinoxaline (
NBQX, 10-50 nmol), an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid (
AMPA) receptors, or of
thiokynurenate (100-400 nmol), which also antagonizes
N-methyl-D-aspartate (
NMDA) receptors, performed immediately after the lesion, significantly reduced this loss. The electron microscope examination showed major damage in each type of retinal neuron, the pigment epithelium, and the microvessels.
NBQX or thiokynurenic
acid reduced, in a comparable manner, the effects of
ischemia on the pigment epithelium, the photoreceptors, and the bipolar and the horizontal cells.
NBQX was particularly efficient in reducing the damage to the amacrine cells located in the inner nuclear layer. The displaced amacrine and
ganglion cells were not protected by
NBQX but were almost completely spared in animals treated with
thiokynurenate. These results show that antagonism of
AMPA receptors is sufficient to reduce ischemic damage in a large number of retinal neurons, but that neuroprotection in the
ganglion cell layer may be obtained only with agents which also antagonize
NMDA receptors.