CHRONIC LOW-DOSE GLUTAMATE IS TOXIC TO RETINAL GANGLION-CELLS - TOXICITY BLOCKED BY MEMANTINE

Purpose. It is well known that acute exposure to high concentrations o f glutamate is toxic to central mammalian neurons. However, the effect of a chronic, minor elevation over endogenous glutamate levels has no t been explored. The authors have suggested that such chronic exposure may play a role in glaucomatous neuronal loss. In the current study, they sought to explore whether a chronic, low-dose elevation in vitrea l glutamate was toxic to retinal ganglion cells and whether this toxic ity could be prevented with memantine, a glutamate antagonist. Methods . Rats were injected serially and intravitreally with glutamate to ind uce chronic elevations in glutamate concentration. A second group of r ats was treated with intraperitoneal memantine and glutamate. Control groups received vehicle injection with or without concurrent memantine therapy. After 3 months, the animals were killed, and ganglion cell s urvival was evaluated, Results. Intravitreal injections raised the int ravitreal glutamate levels from an endogenous range of 5 to 12 mu M gl utamate to 26 to 34 mu M. This chronic glutamate elevation killed 42% of the retinal ganglion cells after 3 months. Memantine treatment alon e had no effect on ganglion cell survival. However, when memantine was given concurrently with low-dose glutamate, memantine was partially p rotective against glutamate toxicity. Conclusions. These data suggest that minor elevations in glutamate concentration can be toxic to gangl ion cells if this elevation is maintained for 3 months. Furthermore, m emantine is efficacious at protecting ganglion cells from chronic low- dose glutamate toxicity.