GENEVIEVE A. NAPPER

MICHAEL KALLONIATIS

Glutamate and γ-aminobutyric acid (GABA) are the 
dominant amino acids in the retina and brain. The manufacturing 
and degradation pathways of both of these amino acids are 
intricately linked with the tricarboxylic acid cycle leading 
to rapid redistribution of these amino acids after metabolic 
insult. Postmortem ischemia in mammalian retina predominantly 
results in a loss of glutamate and GABA from neurons and 
accumulation of these amino acids within Müller cells. 
This accumulation of glutamate and GABA in Müller 
cells may occur as a result of increased release of these 
neurotransmitters from neurons, and decreased degradation. 
Quantification of the semisaturation value (half-maximal 
response) for glutamate and GABA Müller cell loading 
during postmortem ischemia indicated a shorter semisaturation 
value for GABA than glutamate. Such changes are consistent 
with a single aerobically dependent GABA-degradation pathway, 
and the existence of multiple glutamate-degradation pathways. 
Comparison with the in vitro ischemic model showed 
similar qualitative characteristics, but a markedly increased 
semisaturation time for glutamate and GABA Müller 
cell loading (a factor of 5–10) in the postmortem 
ischemia model. We interpret these differences to indicate 
that the in vitro condition provides a more immediate 
and/or severe ischemic insult. In the postmortem ischemia 
model, the delayed glial cell loading implies the availability 
of internal stores of both glucose and/or oxygen. Increased 
glial and neuronal immunoreactivity for the amino acids 
involved in transamination reactions, aspartate, alanine, 
leucine, and ornithine was observed, indicating a potential 
shift in the equilibrium of transamination reactions associated 
with glutamate production. These findings provide evidence 
that, in the rat retina, there are multiple pathways subserving 
glutamate production/degradation that include a multitude 
of transamination reactions. Further evidence is therefore 
provided to support a role for all four amino acids in 
glutamate metabolism within a variety of retinal neurons 
and glia.</jats:p

Neurochemical changes following postmortem ischemia in the rat retina

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