In Vivo Sampling to Study the Neurobiology of Gluacoma

体内取样研究青光眼的神经生物学

• 批准号: 6774101
• 负责人: SCOTT A SHIPPY
• 金额: $ 14.72万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6774101
• 关键词: capillary electrophoresis; eye disorder chemotherapy; eye pharmacology; glaucoma; glutamate transporter; glutamates; intraocular pressure; ion channel blocker; laboratory rat; measurement; neurobiology; ophthalmoscopy; perfusion; potassium chloride; retinal ganglion; sample collection; technology /technique development; vitreous body

DESCRIPTION (provided by applicant): Glaucoma is a neurodegenerative disorder that is the leading cause of blindness in the world. While current treatments are aimed toward reducing the intraocular pressure (lOP), neurodegeneration sometimes continues even with a reduction in lOP. One of the mechanisms that may lead to the selective destruction of retinal ganglion cells is a glutamate-mediated excitotoxicity. Unfortunately, current methods for measuring glutamate in eye tissues do not provide all The desired spatial resolution for characterizing retinal glutamate levels and their potential sources. The goal of this proposal is to develop and demonstrate a novel, in vivo sampling system that provides the needed spatial localization for characterizing vitreal glutamate levels in a rat model of glaucoma. In the first phase of this project, a miniaturized, low-flow push-pull perfusion method and an appropriate capillary electrophoresis assay for glutamate that have been developed in our lab will be adapted for use in the vitreous. The spatial resolution of our low-flow push-pull perfusion will be used to characterize glutamate levels at sites in the central vitreous and vitreoretinal interface. Additionally, the source and dynamics of glutamate levels at the probe tip will be assessed by the inclusion of pharmacological agents into the perfusion solution. In the second phase of this project, the sampling method will be used to address the hypothesis that glutamate levels increase in specific locations at the retina in response to a chronic, moderate increase in lOP in a rat model of glaucoma. Measurements of vitreoretinal glutamate levels will be performed at central and peripheral sites of the retina during the first two weeks of a moderate increase in lOP. The outcomes of this project will be the introduction of a new tool for in vivo sampling in eye tissues and will provide previously inaccessible information regarding the neurobiology of glutamate at the glaucomatous retina. Further, the ability to characterize chemical composition at the retina demonstrated in this study may be applicable to innovative studies of other diseases of the retina.

描述（由申请人提供）：青光眼是一种神经退行性疾病，是世界上导致失明的主要原因。 虽然目前的治疗旨在降低眼内压（IOP），但神经变性有时甚至在IOP降低的情况下仍继续。 可能导致视网膜神经节细胞选择性破坏的机制之一是谷氨酸介导的兴奋性毒性。 不幸的是，目前用于测量眼组织中谷氨酸的方法不能提供用于表征视网膜谷氨酸水平及其潜在来源的所有期望的空间分辨率。 本提案的目标是开发和展示一种新的体内采样系统，该系统提供了表征青光眼大鼠模型中玻璃体谷氨酸水平所需的空间定位。 在本项目的第一阶段，一个小型化，低流量推挽灌注方法和适当的毛细管电泳测定谷氨酸，已在我们的实验室开发将适用于玻璃体。 我们的低流量推挽灌注的空间分辨率将用于表征中心玻璃体和玻璃体视网膜界面部位的谷氨酸水平。 此外，将通过在灌注液中加入药理学试剂来评估穿刺针尖处谷氨酸水平的来源和动力学。 在该项目的第二阶段，将使用采样方法来解决以下假设：在青光眼大鼠模型中，视网膜特定位置的谷氨酸水平响应于lOP的慢性中度增加而增加。在IOP中度增加的前两周期间，将在视网膜的中央和外周部位进行玻璃体视网膜谷氨酸水平的测量。该项目的成果将是引入一种新的工具，用于眼组织的体内采样，并将提供以前无法获得的关于青光眼视网膜谷氨酸盐神经生物学的信息。 此外，在本研究中证明的表征视网膜化学成分的能力可能适用于其他视网膜疾病的创新研究。