EXCITATORY AMINO ACIDS IN GLAUCOMA

描述：大多数青光眼的治疗是针对青光眼的管理。 眼压(IOP)。传统观点认为，过度 眼内压力导致神经节细胞丢失/视神经损伤 在这种疾病中见过。然而，此应用程序中提供的数据， 提示有毒的谷氨酸水平可能导致青光眼视力 损失。谷氨酸和高眼压都会选择性地损害视网膜 视神经的神经节细胞。私家侦探确认了2-3折 青光眼患者玻璃体中谷氨酸的升高。在猴子身上 激光诱导青光眼模型，升高幅度更高(至5-7倍 控制值)。PI已经确定，2-3倍的抬高 大鼠玻璃体中的谷氨酸--当持续较长时间时 时间--可以导致视网膜神经节细胞的丢失 与人类青光眼的情况非常相似。因此，即使 他观察到，谷氨酸的升高只是神经元的副产品 损害--他在青光眼患者体内发现的谷氨酸浓度 玻璃体本身就足以导致神经节细胞丢失。 在这份拨款提案中，他将调查以下假设： (1)中心假说是玻璃体内谷氨酸含量升高 青光眼患者。其他灵长类(人和猴子)的分析 样本可能有助于确定青光眼的诊断是否，或 抗青光眼治疗对谷氨酸升高有一定作用。 (2)他假设过量的谷氨酸来自视网膜， 来自神经节细胞或穆勒细胞。 (3)如果谷氨酸毒性在青光眼的损失中起作用，那么 能阻断谷氨酸损伤可能有效控制青光眼 失明。(3A)他将首先在一个模型中评估谷氨酸拮抗剂 慢性谷氨酸中毒。(3B)如果这些药物阻断成功 慢性谷氨酸毒性，那么(如果谷氨酸毒性在 青光眼)，这些药物也应该延缓青光眼的损失。私人侦探将 因此，在大鼠青光眼模型上测试这些药物。这些实验将 帮助检验中心假设--因为如果一个人能阻止眼压的影响 用谷氨酸拮抗剂升高，那么升高的眼压可能会中毒谷氨酸 神经节细胞损失率。

DESCRIPTION: Most therapy for glaucoma is directed at the management of the intraocular pressure (IOP). Conventional wisdom holds that excessive pressure within the eye leads to the ganglion cell loss/optic nerve damage seen in this disease. The data presented in this application, however, suggest that toxic levels of glutamate can contribute to glaucomatous visual loss. Both glutamate and elevated IOP can selectively damage the retinal ganglion cells of the optic nerve. The PI has identified an 2-3 fold elevation of glutamate in the vitreous of glaucoma patients. In the monkey model of laser-induced glaucoma, the elevation is even higher (to 5-7 times the control values). The PI has established that a 2-3 fold elevation of glutamate in the rat vitreous--when sustained for an extended period of time--can lead to the loss of retinal ganglion cells in a pattern that is very similar to that seen in human glaucoma. Therefore, even if the elevation of glutamate he has observed is simply a byproduct of the neuronal damage-- the concentration of glutamate he has found in glaucomatous vitreous is sufficient on its own to cause ganglion cell loss. In this grant proposal, he will investigate the following hypotheses: (1) The central hypothesis is that glutamate is elevated in the vitreous of glaucoma patients. Analysis of additional primate (human and monkey) samples may help in identifying whether the glaucoma diagnosis, or anti-glaucoma therapy plays a role in glutamate elevation. (2) He hypothesizes that the excess glutamate arises from the retina, either from ganglion or Muller cells. (3) If glutamate toxicity plays a role in glaucomatous loss, then drugs that can block glutamate damage may be effective in controlling glaucomatous blindness. (3A) He will first evaluate glutamate antagonists in a model of chronic glutamate toxicity. (3B) If these drugs are successful at blocking chronic glutamate toxicity, then (if glutamate toxicity is important in glaucoma) these agents should also retard glaucomatous loss. The PI will therefore test these drugs in a rat glaucoma model. These experiments will help test the central hypothesis--for if one can block the effects of IOP elevation with glutamate antagonists, then elevated IOP may toxic glutamate levels ganglion cell loss.