CALCIUM-DEPENDENT FREE-RADICAL GENERATION IN CULTURED RETINAL NEURONSINJURED BY KAINATE

Cultured rat retinal neurons exposed to kainate produced free radicals , as demonstrated by electron spin resonance (ESR) spin trapping using the nitrone 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and the generatio n of DMPO hydroxyl adduct (DMPO-OH). This DMPO-OH production was aboli shed by EGTA, nitro-arginine and oxypurinol, suggesting that it was de pendent on Ca2+ influx and subsequent activation of nitric oxide synth ase and xanthine oxidase. Moreover, kainate induced a receptor-mediate d Ca2+ influx and neuronal injury assessed by lactate dehydrogenase re lease. Neuroprotection afforded by nitro-arginine and oxypurinol shows that calcium-dependent free radical production plays a major role in kainate retinal toxicity.