Background Glutamic acid is an important neurotransmitter of retina.Excessive accumulation will induce neurotoxicity to nervous tissue.A lot of researches of the effect of glutamic acid on retina tissue focus on retinal nerve cells,but its effect on retinal Muller cells is still seldom.Objective Present study was to investigate the effects of glutamic acid on ultrastructure of retinal Muller cells and the expression of glutamine synthetase in cultured retinal Muller cells.Methods Retinal Muller cells were isolated from the eye of 5-to 7-day-old clean Wister rats and cultured in dulbecco’s modification of eagle’s medium dulbecco with 10% calf serum.10,20,50,100,200 μmol/L L-glutamic acid was used in the medium of the third generation of cells for 10 minutes.No L-glutamic acid was used in the normal control group.Cultured Muller cells were identified by immunochemistry to detect the expression of glutamine synthetase.The changes of the ultrastructure of cultured Muller cells were examined under the transmission electron microscope.The expression of glutamine synthetase was semi-quantitatively detected using Western blot.Results Cultured cells showed the consistent shape with the positive reaction for glutamine synthetase in over 95% cells.The Muller cells in normal control group presented the normal cellular organs and ultrastructure.In 10,20,50 μmol/L glumatic acid groups,no obvious change of ultrastructure was found in Muller cells under the transmission electron microscope.Swelling of mitochondrion,agglutination and margination of chromatic in the Muller cells were exhibited in 100 μmol/L glutamic acid group,and vacuoles apoptosis body in the Muller cells could been seen in 200 μmol/L glutamic acid group.Western blot assay revealed that glutamine synthetase was positively expressed in 10,20,50 μmol/L glutamic acid groups and the expression reached the peak at 50 μmol/L glutamic acid groups,and then the expression level of glutamine synthetase declined in 100 and 200 μmol/L glutamic acid groups.The expression levels of glutamine synthetase was significantly higher in 10 μmol/L,20 μmol/L,50 μmol/L,100 μmol/L group glutamic acid group compared with control group (q=29.32,q=75.54,q=48.36,q=130.20,P0.01),and that in 200 μmol/L glutamic acid group was lower than control group(q=46.67,P0.01).Conclusion The dynamic change of expression of glutamine synthetase in Muller cells is related to concentration of glutamic acid.Over 50 μmol/L of glutamic acid causes the damage of ultrastructure of Muller cells. Key words: retina; Muller cell; glutamic acid; glutamine synthetase; ultrastructure