Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells

Iok Hou Pang, Eric M. Wexler, Scott Nawy, Louis DeSantis, Michael A. Kapin

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1170-1176
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume40
Issue number6
StatePublished - May 1 1999

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Retinal Ganglion Cells
Glutamic Acid
N-Methyl-D-Aspartate Receptors
Inhibitory Concentration 50
Retinal Neurons
Excitatory Amino Acid Antagonists
Superior Colliculi
N-Methylaspartate
eliprodil
Fluorescent Dyes
Glaucoma
Cell Survival
Cell Death
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Pang, I. H., Wexler, E. M., Nawy, S., DeSantis, L., & Kapin, M. A. (1999). Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells. Investigative Ophthalmology and Visual Science, 40(6), 1170-1176.

Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells. / Pang, Iok Hou; Wexler, Eric M.; Nawy, Scott; DeSantis, Louis; Kapin, Michael A.

In: Investigative Ophthalmology and Visual Science, Vol. 40, No. 6, 01.05.1999, p. 1170-1176.

Research output: Contribution to journalArticle

Pang, IH, Wexler, EM, Nawy, S, DeSantis, L & Kapin, MA 1999, 'Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells', Investigative Ophthalmology and Visual Science, vol. 40, no. 6, pp. 1170-1176.
Pang, Iok Hou ; Wexler, Eric M. ; Nawy, Scott ; DeSantis, Louis ; Kapin, Michael A. / Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells. In: Investigative Ophthalmology and Visual Science. 1999 ; Vol. 40, No. 6. pp. 1170-1176.
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AU - Kapin, Michael A.

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N2 - 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.

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