RETINAL CHANGES IN GLAUCOMA AND WITH NEUROPROTECTION

青光眼和神经保护的视网膜变化

• 批准号: 6179790
• 负责人: ARTHUR J WEBER
• 金额: $ 22.92万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6179790
• 关键词: Macaca mulatta; cell death; cellular pathology; dendrites; electrophysiology; eye disorder chemotherapy; eye pharmacology; fluorescent dye /probe; glaucoma; intraocular pressure; lateral geniculate body; morphology; neural degeneration; neural transmission; neuroanatomy; neuroprotectants; neurotrophic factors; optic disk; retinal ganglion; visual fields; visual photosensitivity

DESCRIPTION (Adapted from applicant's abstract): Primary open-angle glaucoma (POAG) is a leading cause of blindness in the United States. In many cases, the disease is characterized by an elevation of intraocular pressure (IOP), progressive changes in the appearance of the optic disc and retinal nerve fiber layer, and visual field defects. Over the past several years, a number of studies have described the degenerative effects that chronic elevation of IOP and glaucoma have on fibers in the optic nerve, as well as the concomitant loss of ganglion cells that occurs within the retina itself. More recently, the applicants have combined the monkey model of experimental glaucoma with intracellular staining techniques to examine the morphological changes that characterize glaucomatous neuropathy at the single cell level. These studies showed, for the first time, that the earliest signs of glaucoma-related retinal ganglion cell (RGC) degeneration involves structural abnormalities associated with the dendritic arbors of these neurons. Since retinal ganglion cells receive all of their input from more distal retinal elements through their dendrites, abnormalities in dendritic structure suggest a reduction in synaptic efficacy, and early fractional deficits at the single cell level. A primary goal of the studies proposed here is to use combined anatomical and electrophysiological techniques to determine the extent to which glaucoma-related changes in ganglion cell structure might correlate with changes in ganglion cell function. A second important outcome of the investigator's previous years of work was the finding that morphological changes at the level of the cell body occur later than those at the dendritic tree. This suggests that there is a "window of opportunity" during which the application of neuroprotectants to the diseased visual system might serve to slow or reverse ganglion cell death. Thus, a second goal of the proposed studies is to determine, using a cat optic nerve crush model of retinal ganglion cell atrophy, the extent to which different doses, delivery routes, and delivery rates of brain-derived neurotrophic factor (BDNF), a known neuroprotectant in the small rat eye, might also serve to enhance the survival of ganglion cells in primate-sized eyes and their primary target neurons in the thalamus of the brain.

描述（根据申请人的摘要改编）：主要开放角度 青光眼（POAG）是美国失明的主要原因。 在许多情况下，该疾病的特征是 眼内压（IOP），出现的渐进变化 视盘和视网膜神经纤维层以及视野缺陷。超过 在过去的几年中，许多研究描述了 IOP和青光眼慢性升高对 视神经中的纤维以及伴随的神经节损失 发生在视网膜本身内的细胞。最近， 申请人将实验青光眼的猴子模型与 细胞内染色技术检查形态学变化 这表征了单细胞水平上的青光眼神经病。 这些研究首次表明 青光眼相关的视网膜神经节细胞（RGC）变性涉及 与树突状乔木有关的结构异常 神经元。由于视网膜神经节细胞从 通过其树突，更远端的视网膜元素，异常 树突结构表明突触功效降低，早期 单细胞水平的分数缺陷。一个主要目标 这里提出的研究是使用结合解剖学和 电生理技术以确定多大程度 神经节细胞结构的青光眼相关的变化可能与 神经节细胞功能的变化。第二个重要结果 研究者的往年工作是形态学的发现 细胞体水平的变化比在 树突树。这表明有一个“机会之窗” 在此期间，将神经保护剂应用于患病的视觉 系统可能会减慢或逆转神经节细胞死亡。因此， 拟议的研究的第二个目标是使用CAT Optic确定 视网膜神经节细胞萎缩的神经挤压模型 大脑衍生的不同剂量，输送路线和交付率 神经营养因子（BDNF），小鼠中已知的神经保护剂 眼睛，也可能有助于增强神经节细胞的存活 灵长类大小的眼睛及其主要靶神经元在丘脑中 大脑。