EXCITOTOXIC DAMAGE OF RETINAL GLIAL-CELLS DEPENDS UPON NORMAL NEURON-GLIAL INTERACTIONS

Glutamate, the principal retinal neurotransmitter, can also act as a t oxin when present in excessive concentrations as may occur in patholog ies such as retinal ischemia or more generally in cerebral neuronal de generative disease. As glial cells play pivotal roles in transfer of b lood-borne molecules and in glutamate clearance, we investigated the e ffects of the excitatory amino acids glutamic and kainic acid on diffe rent in vitro preparations of retinal Muller glial cells. Glial viabil ity or morphology were not influenced by excitatory amino acid exposur e in either pure glial cultures or in monolayer cultures of mixed neon atal neurons and glia, whereas kainic acid specifically lysed amacrine cells in mixed or pure neuronal cultures. When retinal fragments were pre-incubated in excitatory amino acids prior to dissociation and see ding into culture, under these conditions Muller glial cells exhibited a dramatic loss of their normal epithelioid form to a retracted morph ology. However, glial cell viability was not compromised, and rapid re storation of epithelioid in vitro glial morphology could be achieved b y addition of exogenous epidermal and basic fibroblast growth factor t o the culture medium. This study demonstrates that glial cells are str ucturally perturbed by excitotoxic conditions and that such effects ar e dependent on normal glial-neuronal interactions. (C) 1998 Wiley-Liss , Inc.