|Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
Cultured retinal glia and neurons are an efficient system to investigate retinal condition after optic nerve transection. The ability of the gliotoxic amino acid, D,L-, D-, L-2-aminoadipic acid (AAA) to increase selectively the intracellular concentration of free calcium ion was examined in Muller cells cultured with or without retinal neurons, by a spectrofluorophotometry using Fura-2. The D,L-and, D-forms of AAA activated neurons at low concentrations and the L-isomer activated Muller cells at low concentrations. The results indicated that AAA,especially the D-isomer, may be an agonist of excitatory amino acid receptor. The next study was focused on glutamate receptor in Muller cells. Cellular response to agonists and antagonists of glutamate receptor was examined similarly. The results indicated that cultured Muller cells possess the AMPA/kainate (non-NMDA) receptor. In the retina without optic nerve, glutamate receptor-linked events are no longer considered as specific to neurons. The action of this receptor may possibly be expressed under pathological rather than physiological conditions. To confirm the hypothesis, the critical concentration in response to the agonist (AMPA) between Muller cells and retinal neurons was compared. AMPA-induced calcium transients occurred in neurons at lower concentration than in Muller cells, suggesting the receptor in Muller cells to act rather pathologically. Furthermore, mhen AMPA at 0.5mM was administered, responsive cell number was higher for cells exposed with a neurotoxic agent, Kainate than control cells.Muller cells may be concluded to resist neurotoxic agents and possibly be involved in survival mechanisms of retinal neurons.