HYDRODYNAMICS OF AQUEOUS HUMOR OUTFLOW

描述（改编自申请人摘要）：总体目标是 确定增加房水流出阻力的主要部位， 原发性开角型青光眼（POAG），在美国是导致失明的主要原因。 作为这些研究的一部分，申请方将评价流出阻力 是在正常人眼中产生的。 人们通常认为， 直接位于施莱姆运河下面的联合指挥中心负责大部分 正常眼的流出阻力， 该区域中细胞外基质（ECM）导致青光眼。 但 并没有直接证明这个命题。 使用速冻/深蚀刻 形态学技术，这个小组现在已经表明，ECM在JCT 比以前认识到的更广泛，可能会产生一个 在正常人眼中，水流出阻力的显著部分。 此应用程序的一个重要方面是使用类似的高级 形态学/形态测量技术，以确定是否流出 POAG中JCT的电阻增加。 这个小组和其他人还表明，特定的血浆衍生蛋白质 会影响房水流出阻力。 他们假设这些蛋白质 与JCT中的ECM相互作用，导致广泛的超微结构 网络看到使用快速冻结/深蚀刻技术，POAG可能 这是由于这些蛋白质在JCT中的过度积累。 的 申请人将测试这一假设，并将检查其他 在正常和肿瘤性JCT组织中发现的大分子，如图所示， 通过快速冷冻/深蚀刻。 虽然他们的研究暗示JCT负责产生 大量的水外流阻力，他们还确定了两种类型 施累姆氏管内壁的孔， 微导管流动阻力。 除了JCT的变化， 青光眼可能部分是由于这些人群中的一个或两个的变化 内壁的气孔。 在本申请中，这种可能性将是 研究了 利用下列领域的综合专门知识 流体动力学、建模、生理学和超微结构， 免疫组织化学方法，本文提出的研究可以显着 提高对房水流出阻力认识及其在 POAG。

DESCRIPTION (Adapted from applicant's abstract): The overall goal is to determine the principle site of increased aqueous outflow resistance in primary open-angle glaucoma (POAG), a leading cause of blindness in the USA. As part of these studies, the applicant will evaluate how outflow resistance is generated in the normal human eye. It is conventionally believed that the JCT immediately underlying Schlemm's canal is responsible for the bulk of outflow resistance in the normal eye, and that changes in the extracellular matrix (ECM) in this region lead to glaucoma. However, there has been no direct proof of this proposition. Using quick-freeze/deep-etch morphological techniques, this group has now shown that the ECM in the JCT is more extensive than previously recognized, and can likely generate a significant fraction of aqueous outflow resistance in the normal human eye. An important aspect of this application is to use similar advanced morphological/morphometric techniques to determine whether the outflow resistance of the JCT is increased in POAG. This group and others have also shown that specific plasma-derived proteins can affect aqueous outflow resistance. They hypothesize that these proteins interact with the ECM in the JCT, leading to the extensive ultrastructural network seen using the quick-freeze/deep-etch techniques, and that POAG may result from excessive accumulation of these proteins in the JCT. The applicant will test this hypothesis, and will also examine other macromolecules found in the normal and glaucomatous JCT tissues, as viewed by quick-freeze/deep-etch. While their studies have implicated the JCT as responsible for generating the bulk of aqueous outflow resistance, they have also identified two types of pores in the inner wall of Schlemm's canal that may modulate juxtacanalicular flow resistance. In addition to changes in the JCT, glaucoma might be in part due to changes in one or both of these populations of inner wall pores. In this application, this possibility will be investigated. Exploiting the combined expertise in the areas of hydrodynamics, modeling, physiology, and ultrastructural and immunohistochemical methods, the studies proposed herein could significantly improve understanding of aqueous outflow resistance and its elevation in POAG.