EXTRACELLULAR MATRIX COMPOSITION OF THE OPTIC NERVE HEAD

了解改变视神经对视觉刺激的反应的因素 眼内压（IOP）将导致青光眼的重要进展 诊断和管理。 通过规定层流的物理行为， 束，视神经乳头细胞外基质（ECM）可能会影响神经 通过允许光束照射到 直接或压缩它们的能力并改变神经纤维 营养 由于初步证据表明眼压升高会改变 视神经头ECM、视神经感受性可在整个过程中发生变化 昏迷的过程 这对临床具有重要意义。 青光眼患者的治疗 本建议将使用光镜和电镜免疫组织化学 描述蛋白聚糖在正常人中的存在和分布， 视神经头 蛋白聚糖是ECM的重要成分， 对细胞-基质相互作用和基质组织的不同影响， 迄今为止，对这种组织的研究很少。 因为无论老少 视神经似乎对升高的IOP有不同的反应， 年龄对蛋白聚糖也将进行研究，以进一步了解 这些大分子在保护视神经纤维中起作用。 免疫组织化学也将用于检测蛋白多糖 分布在脑昏迷的人视神经头中。 这些结果将 与实验性昏迷猴眼进行比较， 青光眼患者眼压升高的影响。 最后，两种临床相关形式的IOP升高，急性高IOP和 慢性中度IOP升高，将在猴眼中产生。 这些眼睛 将被研究并与他们的同伴对照眼进行比较， 利用原位杂交技术合成蛋白聚糖。 此外，本发明还提供了一种方法， 将研究它们的金属蛋白酶分布的变化， 使用免疫组织化学和原位杂交合成， 分别 因为金属蛋白酶被认为是 结缔组织重塑的早期启动者，这些实验提供了 一种高灵敏度的IOP升高试验，作为重塑的刺激， 视神经头ECM。 研究急性和慢性 IOP的升高将建立这些患者的临床条件， 影响发生。

Understanding the factors that modify the optic nerve's response to intraocular pressure (IOP) will lead to important advances in glaucoma diagnosis and management. By dictating the physical behavior of laminar beams, the optic nerve head extracellular matrix (ECM) may affect nerve fiber susceptibihty to elevated IOP by allowing beams to either impinge on nerve fibers directly or compress their capabilities and alter nerve fiber nutrition. Since preliminary evidence suggests that elevated IOP changes the optic nerve head ECM, optic nerve susceptibility may change throughout the glaucomatous process. This has important implications for the clinical management of glaucoma patients. This proposal will use light and electron microscopic immunohistochemistry to delineate the presence and distribution of proteoglycans in the normal optic nerve head. Proteoglycans are important constituents of the ECM with diverse effects on cell-matrix interactions and matrix organization that have to date been little studied in this tissue. Because young and old optic nerves appear to respond to elevated IOP differently, the effects of age on proteoglycans will also be studied to gain further insight into the roles these macromolecules play in protecting optic nerve fibers. Immunohistochemistry will also be used to detect the proteoglycan distribution in glaucomatous human optic nerve heads. These results will be compared to experimentally glaucomatous monkey eyes to separate primary changes in glaucoma patients from the effects of elevated IOP. Finally, two clinically relevant forms of IOP elevation, acute high IOP and chronic moderate IOP elevation, will be created in monkey eyes. These eyes will be studied and compared with their fellow control eyes for changes in the synthesis of proteoglycans using in situ hybridization. In addition, they will be studied for changes in metalloproteinase distribution and synthesis using immunohistochemistry and in situ hybridization, respectively. Because the metalloproteinase enzymes are thought to be early initiators of connective tissue remodeling, these experiments provide a highly sensitive assay of elevated IOP as a stimulus for remodeling of the optic nerve head ECM. Studying the effects of acute and chronic elevations of IOP will establish the clinical conditions under which these effects take place.