May 1999
Volume 40, Issue 6
Free
Articles  |   May 1999
Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells.
Author Affiliations
  • I H Pang
    Alcon Laboratories, Fort Worth, Texas 76134, USA.
  • E M Wexler
    Alcon Laboratories, Fort Worth, Texas 76134, USA.
  • S Nawy
    Alcon Laboratories, Fort Worth, Texas 76134, USA.
  • L DeSantis
    Alcon Laboratories, Fort Worth, Texas 76134, USA.
  • M A Kapin
    Alcon Laboratories, Fort Worth, Texas 76134, USA.
Investigative Ophthalmology & Visual Science May 1999, Vol.40, 1170-1176. doi:
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    • Get Citation

      I H Pang, E M Wexler, S Nawy, L DeSantis, M A Kapin; Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells.. Invest. Ophthalmol. Vis. Sci. 1999;40(6):1170-1176.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

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 microM. Only 47% of RGCs survived after a 3-day treatment with 100 microM 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 microM glutamate). At 1 microM, eliprodil was maximally protective; cell survival in the presence of 100 microM 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.

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