[Dual nature of excitatory amino acids in the vertebrate retina].
Glutamic acid plays an important role as a main excitatory amino acid and also as one of the central metabolites in the central nervous system (CNS). This amino acid also acts as a toxic substance in the vertebrate CNS, including the retina, especially in ischemic conditions. This paper reviews recent advances in retinal research on glutamate metabolism and its relationship with pathogenesis of retinal diseases. Excessive administration of glutamate induces overstimulation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and influx of Na+, Cl-, and water to postsynaptic elements, causing lysis and swelling. In hypoxic or ischemic conditions, accumulation of glutamate was observed in most parts of the retina. Morphological and functional changes induced by ischemia could be prevented by preadministration of an antagonist of NMDA receptors. These results suggest that the same pathological mechanism as in the CNS exists in the retina. They also suggest that a new pharmacological approach for treating retinal abnormalities caused by ischemia could be introduced in the ophthalmology clinic in the near future. Abnormality of glutamate dehydrogenase, an important enzyme in the glutamate metabolism, has been reported in patients with spinocerebellar degenerations. Retinal dystrophy was also reported in some of them. Partial deficiency of heat-labile activity of this enzyme has been reported to be profoundly related with those patients with retinal abnormalities. This suggests that not only glutamate itself, but also abnormalities in its metabolic path way might be deeply correlated with the pathogenesis of retinal degeneration.
Tamai
M
M
Department of Ophthalmology, Tohoku University School of Medicine, Miyagi-ken, Japan.
D000818:Animals; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*; D012164:Retinal Diseases / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates