TURNOVER OF SUBSTANCES IN THE OUTFLOW PATHWAY OF THE EYE

调节水分外流的精确机制是 未知，但小梁细胞之间的相互作用 网络，它们的底层胶原梁和其他 细胞外物质(包括糖胺多聚糖)可能起作用 一个重要的角色。这些细胞，由于它们的吞噬特性， 能够清除前部的碎片或颗粒 被困在网状结构的孔隙中的腔室， 从而影响眼压。新陈代谢的变化 这些细胞的状态由于衰老、药物、激素、 环境或其他影响可能会导致人员更替 减少内源性和外源性物质，减少水份 流出设施。拟议研究的目标是评估 吞噬小体/溶酶体介导人血管内皮细胞的作用 小梁细胞在调节胃液流出设施中的作用 人、猴和牛眼的小梁细胞 将被保存在文化中。它们吞噬细胞的速度 包括红色镜片材料在内的各种放射性标记颗粒的细胞 血细胞和富含蛋白质的乳胶球将被测定。 颗粒所涉及的小梁细胞表面成分 识别和摄取蛋白将由细胞表面识别 放射性标记及放射性碘标记和荧光素标记凝集素 约束性研究。小梁细胞的化学修饰 表面或在骨小梁上添加各种物质 吞噬之前的细胞或伴随吞噬的细胞可提供 对影响粒子识别的因素和 摄取。溶酶体降解颗粒的动力学研究 将检查酶以及吞噬作用对 从细胞中合成和释放这些酶。这个 溶酶体酶也可能在体内发挥重要作用 小梁网内源性材料的周转和 从而有助于调节眼压。酶 沙门氏菌溶酶体酶的活性和生化性质 正常人和青光眼切除的人眼小梁组织 两只眼睛将被比较。此外，还建议进行以下研究： 研究猪溶酶体酶的生化特性 并确定影响其生长的因素。 细胞定位和细胞外定位。这一机制通过它 这些酶是针对溶酶体和细胞外液的。 将通过确定碳水化合物的类型来进行研究 小梁细胞溶酶体酶的结构。这个 猪溶酶体酶的定位和生化特性 培养的小梁细胞也将在治疗后进行评估 已知会影响眼内的实验药物 压力。

The precise mechanism by which aqueous outflow is regulated is not known but interactions between the cells of the trabecular meshwork, their underlying collagen beams and other extracellular substances (including glycosaminoglycans) may play an important role. These cells, given their phagocytic properties, are capable of removing debris or particles in the anterior chamber that become trapped in the pores of the meshwork, thereby affecting intraocular pressure. A change in the metabolic state of these cells due to the effects of aging, drugs, hormones, environment or other influences may lead to an altered turnover of endogenous and foreign substances and decrease aqueous outflow facility. The goal of the proposed research is to evaluate the role of phagosome/lysosome-mediated events of the trabecular cells in regulating agueous outflow facility. Trabecular cells obtained from human, monkey and bovine eyes will be maintained in culture. The rate of phagocytosis by these cells of various radiolabeled particles including lens material, red blood cells and protein-laden latex spheres will be determined. The trabecular cell surface components involved in particle recognition and ingestin will be identified by cell surface radiolabeling and by radio-iodinated and fluorscein-labeled lectin binding studies. Chemical modification of the trabecular cell surface or the addition of various substances to the trabecular cells prior to or concomitant with phagocytosis may provide insights regarding factors that effect particle recognition and ingestion. The kinetics of particle degradation by the lysosomal enzymes will be examined as well as the effect of phagocytosis on the synthesis and release of these enzymes from the cells. The lysosomal enzymes may also play an important role in the turnover of material endogenous to the trabecular meshwork and thus contribute to the regulation of intraocular pressure. Enzyme activities and biochemical properties of lysosomal enzymes from human trabecular tissue excised from normal and glaucomatous eyes will be compared. In addition, studies are proposed to investigate the biochemical properties of lysosomal enzymes in trabecular cells and to determine factors that influence their cellular and extracellular localization. The mechanism by which these enzymes are targeted to lysosomes and extracellular fluids will be investigated by determining the types of carbohydrate structure on the lysosomal enzymes from trabecular cells. The localization and biochemical properties of lysosomal enzymes in cultured trabecular cells will also be evaluated after treatment with experimental agents that are known to affect intraocular pressure.