Hains Bryan C, Waxman Stephen G
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4164-9. doi: 10.1167/iovs.05-0618.
Sustained influx of intracellular sodium through voltage-gated sodium channels is an important event in the cascade leading to degeneration of axons. This study tested the hypothesis that sodium channel blockade with phenytoin would result in neuroprotection of retinal ganglion cells (RGCs) and optic nerve axons in an experimental model of glaucoma.
Chronic elevation of rat intraocular pressure (IOP) leading to optic nerve damage was induced using the episcleral vein occlusion model. Before induction of glaucoma, a subset of animals was placed on phenytoin-containing chow; this treatment continued for 8 weeks. Quantitative counts of backfilled RGCs and optic nerve axons was performed to examine the effects of phenytoin on glaucoma-induced adverse neurodegeneration.
Elevated IOP resulted in a significant decrease in density of RGCs, as well as dropout of axons within the optic nerve at 8 weeks after induction. In phenytoin-treated animals, however, the loss of RGCs was significantly reduced compared to vehicle-treated glaucomatous animals. Axon loss in the optic nerve was also reduced in phenytoin-treated animals, compared to controls.
Orally delivered phenytoin was effective in protecting neurons in an animal model of glaucoma, and merits further examination as a potential therapeutic strategy.
通过电压门控钠通道持续内流的细胞内钠是导致轴突退变级联反应中的一个重要事件。本研究检验了如下假设：在青光眼实验模型中，用苯妥英钠阻断钠通道可对视网膜神经节细胞（RGCs）和视神经轴突起到神经保护作用。
采用巩膜静脉阻塞模型诱导大鼠眼压（IOP）慢性升高，从而导致视神经损伤。在诱导青光眼之前，将一部分动物置于含苯妥英钠的食物中；这种治疗持续8周。对逆向标记的RGCs和视神经轴突进行定量计数，以检查苯妥英钠对青光眼诱导的不良神经退变的影响。
眼压升高导致诱导后8周时RGCs密度显著降低，以及视神经内轴突缺失。然而，与接受载体治疗的青光眼动物相比，在接受苯妥英钠治疗的动物中，RGCs的损失显著减少。与对照组相比，接受苯妥英钠治疗的动物视神经中的轴突损失也减少了。
口服苯妥英钠在青光眼动物模型中对神经元具有保护作用，作为一种潜在的治疗策略值得进一步研究。
