GREATER SENSITIVITY OF LARGER RETINAL GANGLION-CELLS TO NMDA-MEDIATED CELL DEATH

GLUTAMATE toxicity in retinal ganglion cells has well documented both in vitro and in vivo, and has been suggested to play a role in the neuronal loss in glaucoma. Of note, glaucoma selectively damages larger retinal ganglion cells first, and we therefore sought to explore whether glutamate-mediated cell death was likewise more pronounced in larger retinal ganglion cells. We now report that glutamate-which exerts its toxic effect on neurons predominantly through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor-is more toxic to larger retinal ganglion cells both in tissue culture and in the intact rat eye. Cells smaller than 10 mu m were relatively unaffected by glutamate or NMDA. These agents are, however, markedly toxic to retinal ganglion cells larger than 10 mu m. These observations indicate that glutamate-mediated loss is seen first in larger retinal ganglion cells, in a similar fashion to the pattern of loss seen in glaucoma.