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.
