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 EC50 of 10.7 μM. Only 47% of RGCs survived after a 3- day treatment with 100 μM 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 IC50 of 1.0 nM (log [IC50] = - 9.00 ± 0.01, mean ± SEM, n = 3; against cell death produced by 100 μM glutamate). At 1 μM, eliprodil was maximally protective; cell survival in the presence of 100 μM 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.
|Number of pages||7|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - 1 May 1999|