EXTRACELLULAR MATRIX COMPOSITION OF THE OPTIC NERVE HEAD

了解影响视神经反应的因素 眼压(IOP)将导致青光眼的重要进展 诊断和管理。通过口述层流的物理行为 BEAM、视神经头细胞外基质(ECM)可能影响神经 光纤对高眼压的敏感性，因为它允许光束撞击 神经纤维直接或压迫它们的能力并改变神经纤维 营养。因为初步证据表明眼压升高会改变 视神经头细胞外基质，视神经敏感度可能会始终改变 青光眼的过程。这对临床治疗有重要意义。 青光眼患者的管理。 这项提议将使用光镜和电子显微镜免疫组织化学 描述正常人群中蛋白多糖的存在和分布 视神经头。蛋白多糖是细胞外基质的重要成分，具有 对细胞-基质相互作用和基质组织的不同影响 到目前为止在这个组织中的研究还很少。因为老老少少 视神经似乎对高眼压的反应不同， 对蛋白多糖的年龄也将进行研究，以进一步了解 这些大分子在保护视神经纤维方面扮演着重要角色。 免疫组织化学也将被用来检测蛋白多糖 青光眼患者视神经头的分布。这些结果将 与实验性青光眼猴眼分离比较 青光眼患者眼压升高的变化。 最后，两种临床相关的眼压升高形式，急性高眼压和 慢性中度眼压升高，会在猴眼中产生。这双眼睛 会被研究并与他们的同伴对照眼球的变化 用原位杂交法合成蛋白多糖。此外, 他们将被研究金属蛋白酶分布的变化和 用免疫组织化学和原位杂交合成， 分别进行了分析。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 高眼压作为眼压重塑刺激因素的高灵敏度分析 视神经头细胞外基质。研究急性和慢性疾病的影响 眼压升高将建立临床条件，在这种情况下 效果就会发生。

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.