Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions

The high-affinity uptake of glutamate by glial cells and neurons of the cen tral nervous system, including the retina, serves to inactivate synapticall y released glutamate and maintains glutamate at low concentrations in the e xtracellular space. This uptake prevents accumulation of glutamate extracel lularly and thus minimizes the possibility of glutamate neurotoxicity secon dary to ischemic insult. One mechanism whereby glutamate neurotoxicity may occur in ischemic/hypoxic insult is through increased extracellular K+ reve rsing the electrogenic glutamate uptake into retinal glial (Muller) cells. We investigated glial uptake of the amino acids glutamate, GABA, and D-aspa rtate in the intact isolated rat retina under high extracellular K+ conditi ons and under conditions simulating ischemia. Immunocytochemical findings s howed that uptake of glutamate and GABA by Muller cells in the intact isola ted rat retina continues under conditions simulating ischemia and high extr acellular K+ conditions, and uptake of D-aspartate also continues under hig h K+ conditions. However, under high K+ conditions, the glutamate uptake sy stem saturates at a lower concentration of exogenous glutamate than in the normal K+ condition. These findings provide evidence that disruption of glu tamate uptake by Muller cells is likely to be a significant contributing fa ctor to excess glutamate accumulation in the extracellular space which can lead to neurotoxicity.