HYDRODYNAMICS OF AQUEOUS HUMOR OUTFLOW

描述(改编自申请者摘要)：总体目标是 确定水溶液流出阻力增大的主要位置 原发性开角型青光眼(POAG)是美国导致失明的主要原因。 作为这些研究的一部分，申请者将评估流出阻力 是在正常的人眼中产生的。人们通常认为 紧挨着Schlemm运河下面的JCT对大块负责 在正常眼睛中的流出阻力，这在 该区域的细胞外基质(ECM)可导致青光眼。然而，在那里 并没有直接证明这一命题。使用快速冷冻/深度蚀刻 形态技术，这个小组现在已经证明了ECM在JCT 比以前认识到的更广泛，并且很可能会生成 正常人眼房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/形态测量技术来确定外流是否 POAG患者的JCT阻力增大。 该小组和其他人还表明，特定的血浆衍生蛋白 会影响水的流出阻力。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 使用快速冻结/深蚀刻技术观察到的网络，以及POAG可能 这是由于这些蛋白质在JCT中过度积累所致。这个 申请者将检验这一假设，还将检验其他 在正常和青光眼JCT组织中发现的大分子 通过快速冷冻/深度蚀刻。 虽然他们的研究表明联合技术委员会负责产生 大部分的水流出阻力，他们还确定了两种类型 在Schlemm管内壁上可能调节 管旁流动阻力。除了联合技术条约的变化外， 青光眼可能在一定程度上是由于这两个人群中的一个或两个发生了变化 内壁的毛孔。在此应用程序中，此可能性将是 调查过了。利用以下领域的综合专业知识 流体动力学、建模、生理学、超微结构和 免疫组织化学方法，这里提出的研究可以显著地 提高对水中流出阻力及其升高的理解 普阿格。

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.