Phenytoin blocks retinal ganglion cell death after partial optic nerve crush

Rita Naskar; Kristine Quinto; Ilka Romann; Frank Schuettauf; David Zurakowski

doi:10.1006/exer.2002.1173

Phenytoin blocks retinal ganglion cell death after partial optic nerve crush

Standard

Phenytoin blocks retinal ganglion cell death after partial optic nerve crush. / Naskar, Rita; Quinto, Kristine; Romann, Ilka; Schuettauf, Frank; Zurakowski, David.

In: EXP EYE RES, Vol. 74, No. 6, 06.2002, p. 747-52.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Naskar, R, Quinto, K, Romann, I, Schuettauf, F & Zurakowski, D 2002, 'Phenytoin blocks retinal ganglion cell death after partial optic nerve crush', EXP EYE RES, vol. 74, no. 6, pp. 747-52. https://doi.org/10.1006/exer.2002.1173

APA

Naskar, R., Quinto, K., Romann, I., Schuettauf, F., & Zurakowski, D. (2002). Phenytoin blocks retinal ganglion cell death after partial optic nerve crush. EXP EYE RES, 74(6), 747-52. https://doi.org/10.1006/exer.2002.1173

Vancouver

Naskar R, Quinto K, Romann I, Schuettauf F, Zurakowski D. Phenytoin blocks retinal ganglion cell death after partial optic nerve crush. EXP EYE RES. 2002 Jun;74(6):747-52. https://doi.org/10.1006/exer.2002.1173

Bibtex

@article{5e9d3416c6be48349729943af3e24079,

title = "Phenytoin blocks retinal ganglion cell death after partial optic nerve crush",

abstract = "Phenytoin is a well-characterized sodium channel blocker in widespread use as an anticonvulsant. In 1972, Becker and co-workers reported that phenytoin could reverse visual field loss from glaucoma. The authors therefore explored whether phenytoin could protect retinal ganglion cells from optic nerve crush. The optic nerve of Long-Evans rats was partially crushed; animals were given a single dose of either intraperitoneal phenytoin or vehicle. A third group underwent sham optic nerve crush. In a second set of experiments, the effect of phenytoin was compared to the N -methyl- D -receptor antagonist, memantine. Retinal ganglion survival was evaluated 1 week later. In addition, the effect of memantine and phenytoin on glutamate-induced intracellular calcium fluxes was evaluated.Phenytoin and memantine significantly reduced ganglion cell loss after optic nerve crush, and blunted the rise in intracellular calcium seen after administration of glutamate. Co-administration of the two agents, however, did not increase ganglion cell survival, and had no effect on ganglion cell calcium fluxes. Phenytoin can preserve retinal ganglion cells after partial optic nerve crush. This effect was not additive with a glutamate antagonist, suggesting that both agents alone are equally protective at saving the same population of ganglion cells at risk. In fact, the neuroprotective effect of the combined administration of phenytoin and memantine was significantly less than either of the two drugs alone. Phenytoin is known to decrease neuronal firing and neurotransmitter release; this may underlie its ability to serve as a neuro-protectant in this experimental paradigm.",

keywords = "Analysis of Variance, Animals, Calcium/metabolism, Cell Death/drug effects, Cell Survival/drug effects, Drug Therapy, Combination, Excitatory Amino Acid Antagonists/therapeutic use, Female, Memantine/therapeutic use, Nerve Crush, Neuroprotective Agents/therapeutic use, Optic Nerve Injuries/drug therapy, Phenytoin/therapeutic use, Rats, Rats, Long-Evans, Retinal Ganglion Cells/drug effects",

author = "Rita Naskar and Kristine Quinto and Ilka Romann and Frank Schuettauf and David Zurakowski",

year = "2002",

month = jun,

doi = "10.1006/exer.2002.1173",

language = "English",

volume = "74",

pages = "747--52",

journal = "EXP EYE RES",

issn = "0014-4835",

publisher = "Academic Press Inc.",

number = "6",

}

RIS

TY - JOUR

T1 - Phenytoin blocks retinal ganglion cell death after partial optic nerve crush

AU - Naskar, Rita

AU - Quinto, Kristine

AU - Romann, Ilka

AU - Schuettauf, Frank

AU - Zurakowski, David

PY - 2002/6

Y1 - 2002/6

N2 - Phenytoin is a well-characterized sodium channel blocker in widespread use as an anticonvulsant. In 1972, Becker and co-workers reported that phenytoin could reverse visual field loss from glaucoma. The authors therefore explored whether phenytoin could protect retinal ganglion cells from optic nerve crush. The optic nerve of Long-Evans rats was partially crushed; animals were given a single dose of either intraperitoneal phenytoin or vehicle. A third group underwent sham optic nerve crush. In a second set of experiments, the effect of phenytoin was compared to the N -methyl- D -receptor antagonist, memantine. Retinal ganglion survival was evaluated 1 week later. In addition, the effect of memantine and phenytoin on glutamate-induced intracellular calcium fluxes was evaluated.Phenytoin and memantine significantly reduced ganglion cell loss after optic nerve crush, and blunted the rise in intracellular calcium seen after administration of glutamate. Co-administration of the two agents, however, did not increase ganglion cell survival, and had no effect on ganglion cell calcium fluxes. Phenytoin can preserve retinal ganglion cells after partial optic nerve crush. This effect was not additive with a glutamate antagonist, suggesting that both agents alone are equally protective at saving the same population of ganglion cells at risk. In fact, the neuroprotective effect of the combined administration of phenytoin and memantine was significantly less than either of the two drugs alone. Phenytoin is known to decrease neuronal firing and neurotransmitter release; this may underlie its ability to serve as a neuro-protectant in this experimental paradigm.

AB - Phenytoin is a well-characterized sodium channel blocker in widespread use as an anticonvulsant. In 1972, Becker and co-workers reported that phenytoin could reverse visual field loss from glaucoma. The authors therefore explored whether phenytoin could protect retinal ganglion cells from optic nerve crush. The optic nerve of Long-Evans rats was partially crushed; animals were given a single dose of either intraperitoneal phenytoin or vehicle. A third group underwent sham optic nerve crush. In a second set of experiments, the effect of phenytoin was compared to the N -methyl- D -receptor antagonist, memantine. Retinal ganglion survival was evaluated 1 week later. In addition, the effect of memantine and phenytoin on glutamate-induced intracellular calcium fluxes was evaluated.Phenytoin and memantine significantly reduced ganglion cell loss after optic nerve crush, and blunted the rise in intracellular calcium seen after administration of glutamate. Co-administration of the two agents, however, did not increase ganglion cell survival, and had no effect on ganglion cell calcium fluxes. Phenytoin can preserve retinal ganglion cells after partial optic nerve crush. This effect was not additive with a glutamate antagonist, suggesting that both agents alone are equally protective at saving the same population of ganglion cells at risk. In fact, the neuroprotective effect of the combined administration of phenytoin and memantine was significantly less than either of the two drugs alone. Phenytoin is known to decrease neuronal firing and neurotransmitter release; this may underlie its ability to serve as a neuro-protectant in this experimental paradigm.

KW - Analysis of Variance

KW - Animals

KW - Calcium/metabolism

KW - Cell Death/drug effects

KW - Cell Survival/drug effects

KW - Drug Therapy, Combination

KW - Excitatory Amino Acid Antagonists/therapeutic use

KW - Female

KW - Memantine/therapeutic use

KW - Nerve Crush

KW - Neuroprotective Agents/therapeutic use

KW - Optic Nerve Injuries/drug therapy

KW - Phenytoin/therapeutic use

KW - Rats

KW - Rats, Long-Evans

KW - Retinal Ganglion Cells/drug effects

U2 - 10.1006/exer.2002.1173

DO - 10.1006/exer.2002.1173

M3 - SCORING: Journal article

C2 - 12126947

VL - 74

SP - 747

EP - 752

JO - EXP EYE RES

JF - EXP EYE RES

SN - 0014-4835

IS - 6

ER -