NEURONAL CHANGES IN THE RETINA AND THALAMUS IN GLAUCOMA

青光眼视网膜和丘脑的神经元变化

• 批准号: 2165456
• 负责人: ARTHUR J WEBER
• 金额: $ 19.89万
• 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 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2165456
• 关键词: Macaca mulatta; cell death; cellular pathology; dendrites; fluorescent dye /probe; glaucoma; lateral geniculate body; morphology; neural degeneration; retinal ganglion; soma; Macaca mulatta; cell death; cellular pathology; dendrites; fluorescent dye /probe; glaucoma; lateral geniculate body; morphology; neural degeneration; retinal ganglion; soma

Primary open-angle glaucoma (POAG) is a leading cause of blindness. Clinically, most cases of POAG are characterized by an increase in intraocular pressure (IOP), progressive changes in the structure of the optic disc, and visual field defects. While numerous studies have focused on the degenerative effects that chronic elevation of IOP has on fibers in the optic nerve, few data are available concerning the pattern or the time course of glaucomatous neuropathy that occurs within the primate retina or its central target, the dorsal lateral geniculate nucleus (LGN). The overall goal of the proposed research is to define the temporal relation between the onset and progression of glaucoma measured clinically, and the degeneration of retinal ganglion cells and LGN neurons. Since no previous glaucoma-related study has examined the morphology of single ganglion cells, a necessary first step is to identify those structural features that characterize ganglion cell degeneration in the glaucomatous eye. To do this, the somata and dendritic fields of ganglion cells in the retinae of normal monkeys and monkeys with clinically well-defined, experimentally-induced, glaucoma will be compared by labeling single ganglion cells intracellularly in an in vitro retinal preparation. Once the structural features characteristic of ganglion cell degeneration are defined, the next series of experiments will determine the duration of increased intraocular pressure that produces the earliest detectable changes in ganglion cell morphology. Single ganglion cells will be injected in the retinae of monkeys that have had the pressure in one eye elevated for a period of time ranging from 2 weeks to 3 months. The focus of these experiments, which is the central goal of the proposed studies, is to define the temporal relation between clinically recognizable glaucomatous neuropathy and the onset and progression of retinal ganglion cell degeneration, thus establishing the level of neuronal damage that may precede, as well as accompany, the clinical stages of the disease. The proposed work also will address the possibility that glaucoma affects different classes of ganglion cells, and therefore different functional visual channels selectively. Previous studies, based on Niss1-staining of cell bodies, have suggested that large ganglion cells (presumably parasol cells-M pathway) may be more vulnerable than the smaller, midget, ganglion cells (P pathway). Since intracellular dye injection stains not only the cell body but also the dendritic tree of ganglion cells, the proposed experiments make it possible to determine unequivocally whether parasol cells are affected preferentially during the early stages of glaucoma. Further, since midget and parasol cells project to different layers of the LGN, comparison of the neuronal changes in the parvo- and magnocellular layers of the LGN, which receive input from midget and parasol ganglion cells respectively, will provide additional information regarding possible selective effects of glaucoma. Because the M and P pathways subserve different visual functions, the results of these experiments have the potential to direct the future development of more sensitive and specific tests for the early detection of glaucoma. The results also will serve as the basis for later exploring new treatments aimed at mitigating or preventing glaucoma-induced ganglion cell degeneration, by delivering neuroprotectants to the glaucomatous eye.

原发性开角青光眼（POAG）是失明的主要原因。 在临床上，大多数POAG病例的特征是增加 眼内压（IOP），结构的进行性变化 视光盘和视野缺陷。众多研究集中 关于IOP慢性升高对纤维的退化作用 视神经，几乎没有关于模式或时间的数据 在灵长类动物视网膜内发生的青光眼神经病病程或 它的中心靶标，背侧侧向核（LGN）。 拟议研究的总体目标是定义时间范围 测量的青光眼的发作和进展之间的关系 临床上，视网膜神经节细胞和LGN的变性 神经元。由于先前没有青光眼相关的研究已经检查了 单神经节细胞的形态，必须的第一步是识别 那些表征神经节细胞变性的结构特征 青光眼的眼睛。为此，索马塔和树突状田地 正常猴子和猴子的视网膜中的神经节细胞与 将比较临床定义明确的，实验性诱导的青光眼 通过在体外视网膜中细胞细胞内标记单神经节细胞 准备。曾经的结构特征是神经节细胞的特征 定义了变性，下一系列实验将确定 最早产生的眼内压增加的持续时间 神经节细胞形态的可检测变化。单神经节细胞将 被注射在一个有压力的猴子的视网膜中 眼睛升高了一段时间，范围为2周到3个月。这 这些实验的重点，这是提议的核心目标 研究是为了定义临床上的时间关系 可识别的青光眼神经病以及发作和进展 视网膜神经节细胞变性，因此建立了 可能在临床上及其伴随的神经元损害 疾病的阶段。 拟议的工作还将解决青光眼影响的可能性 不同类别的神经节细胞，因此不同的功能 视觉频道有选择地。先前的研究，基于NISS1染色 细胞体提出了大的神经节细胞（大概是parasol Cells-M途径）可能比较小的侏儒，神经节更脆弱 细胞（P途径）。由于细胞内染料注入不仅 细胞体，也是神经节细胞的树突树，提出了 实验使得可以明确确定parasol是否 在青光眼的早期阶段，优先影响细胞。 此外，由于侏儒和阳伞细胞将其投影到不同层的不同层 LGN，parvo和大细胞的神经元变化的比较 LGN的层，收到来自Midget和Parasol神经节的输入 细胞分别将提供有关可能的其他信息 青光眼的选择性作用。因为M和P途径需要 不同的视觉功能，这些实验的结果具有 指导更敏感和更具体的未来发展的潜力 早期检测青光眼的测试。结果也将作为 以后探索旨在减轻或 通过交付 神经保护剂到青光眼的眼睛。