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Abstract #5447 Published in IGR 1-2

Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells

Pang I-H; Wexler EM; Nawy S; DeSantis L; Kapin MA
Investigative Ophthalmology and Visual Science 1999; 40: 1170-1176


PURPOSE: To test whether eliprodil (SL 82.0715), a unique antagonist for the N-methyl-D-aspartate (NMDA) receptor, is protective in the glutamate- induced cytotoxicity model in cultured rat retinal ganglion cells (RGCs). METHODS: Two to four days after a fluorescent dye, Di-I, was injected near the superior colliculi, neonatal rats were killed, and retinal cells were dissociated and cultured. Survival of RGCs after drug treatment was assayed by counting Di-I fluorescent cells. RESULTS: In rat RGCs, glutamate-induced toxicity with a mean EC sub(50) of 10.7 mu M. Only 47% of RGCs survived after a 3- day treatment with 100 mu M glutamate. Studies using selective agonists and antagonists indicated that the glutamate-induced toxicity was mediated largely by the NMDA receptor. Pretreatment with eliprodil protected against such toxicity. Eliprodil exhibited a mean IC sub(50) of 1.0 nM (log IC sub(50)] = - 9.00 +- 0.01, mean +- SEM, n = 3; against cell death produced by 100 mu M glutamate). At 1 mu M, eliprodil was maximally protective; cell survival in the presence of 100 mu M glutamate challenge was 100% +- 5% (n = 3). This protective effect of eliprodil may be related to its reduction (by 78%) of NMDA-induced currents recorded under patch-clamp recording in these cells. CONCLUSIONS: Eliprodil is protective against glutamate cytotoxicity in retinal neurons. It may be a useful novel compound for the treatment of retinopathies including glaucoma in which excitotoxicity has been implicated.

I.-H. Pang, Alcon Laboratories, 6201 South Freeway, Fort Worth, TX 76134; United States


Classification:

11.8 Neuroprotection (Part of: 11 Medical treatment)



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