Glutamate regulates the viability of retinal cells in culture

In this study, we show that glutamate regulates the viability of cultured r etinal cells upon transient glucose deprivation. At low concentrations (10- 100 muM) glutamate decreased MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] reduction to about 50% of control and decreased intrac ellular ATP levels (about 4-fold) after transient glucose removal. Under th ese conditions, the decrease in MTT reduction was associated with the activ ation of NMDA (N-methyl-D-aspartate) receptors. Upon exposure to high (10 m M) glutamate and transient glucose deprivation, the intracellular levels of glutamate increased. High glutamate significantly counteracted the decreas e in MTT reduction and ATP production observed in the presence of low gluta mate concentrations. AOAA (aminooxyacetic acid), a non-specific inhibitor o f mitochondrial transaminases, enhanced the intracellular glutamate levels, but did not largely affect glutamate-mediated changes in MTT reduction or ATP production. Furthermore, the intracellular levels of pyruvate were not significantly altered, suggesting that changes in ATP production were not d ue to an increase in glycolysis. Thus, the recovery from glucose deprivatio n seems to be facilitated in retinal neuronal cells that had been exposed t o high glutamate, in comparison with low glutamate, suggesting a role for h igh glutamate and glucose in maintaining retinal cell function following co nditions of glucose scarcity. (C) 2001 Elsevier Science Ltd. All rights res erved.