Phenytoin blocks retinal ganglion cell death after partial optic nerve crush
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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, Jahrgang 74, Nr. 6, 06.2002, S. 747-52.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -