Neurochemical changes following postmortem ischemia in the rat retina

Glutamate and gamma-aminobutyric acid (GABA) are the dominant amino acids i n the retina and brain. The manufacturing and degradation pathways of both of these amino acids are intricately linked with the tricarboxylic acid cyc le leading to rapid redistribution of these amino acids after metabolic ins ult. Postmortem ischemia in mammalian retina predominantly results in a los s of glutamate and GABA from neurons and accumulation of these amino acids within Muller cells. This accumulation of glutamate and GABA in Muller cell s may occur as a result of increased release of these neurotransmitters fro m neurons, and decreased degradation. Quantification of the semisaturation value (half-maximal response) for,glutamate and GABA Muller cell loading du ring postmortem ischemia indicated a shorter semisaturation value for GABA than glutamate. Such changes are consistent with a single aerobically depen dent GABA-degradation pathway, and the existence of multiple glutamate-degr adation pathways. Comparison with the in vitro ischemic model showed simila r qualitative characteristics, but a markedly increased semisaturation time for glutamate and GABA Muller cell loading (a factor of 5-10) in the postm ortem ischemia model. We interpret these differences to indicate that the i n vitro condition provides a more immediate and/or severe ischemic insult. In the postmortem ischemia model, the delayed glial cell loading implies th e availability of internal stores of both glucose and/or oxygen. Increased glial and neuronal immunoreactivity for the amino acids involved in transam ination reactions, aspartate, alanine, leucine, and ornithine was observed, indicating a potential shift in the equilibrium of transamination reaction s associated with glutamate production. These findings provide evidence tha t, in the rat retina, there are multiple pathways subserving glutamate prod uction/degradation that include a multitude of transamination reactions. Fu rther evidence is therefore provided to support a role for all four amino a cids in glutamate metabolism within a variety of retinal neurons and glia.