HYDRODYNAMICS OF AQUEOUS HUMOR OUTFLOW

我们的主要目标是确定抵抗的主要地点 房水从正常眼流出，并确定如何 原发性开角型青光眼(POAG)的抵抗力发生改变。我们有 最近发现了水的几个新的基本特征 似乎具有重要的水动力影响的流出系统。 其中有一种以前未被认识到的流体动力相互作用，即 内壁内皮毛孔间的“漏斗”效应 Schlemm管和邻近结缔组织(JCT) 可能会大大增加这一区域的流动阻力。我们计划 通过结合灌流确定这一现象的重要性 对“漏斗”区域的研究、形态计量检验 效果明显，并对工程多孔介质进行了分析。 我们小组的进一步发现是，水中的大部分蛋白质 幽默是通过虹膜的根部进入的，而不是传统的 思想，穿过后房。紧邻这一点 小梁网络的蛋白质入口点(TM)提高了 骨小梁间的蛋白质浓度 空间可能比之前猜测的要高得多。首字母 牛眼的实验研究已经证明了流体力学 这种额外的蛋白质负荷的含义，并表明这些蛋白质 可能有助于正常维持牛的流出阻力。 在非人类实验中发生的流出阻力的减少 灌流(“冲刷”)现在可以解释和预防。我们计划 更深入地探索这一发现，并确定其与 人类流出生理学。 最后，就像在其他结缔组织中发生的那样，我们已经展示了一种 TM中与年龄相关的糖胺聚糖的减少，并假设 这一下降可能具有重要的物理化学流体动力学 后果可能包括组织表面疏水性增加 导致胶原纤维结合和亲脂性吸附 蛋白质。使用形态技术，包括荧光， 疏水探针，我们将确定这些变化的程度 POAG；并且，我们将实验性地修改水的流出路径以 模拟这些变化并确定它们对含水流出的影响 动力学。 利用我们在建模领域的综合专业知识， 流体动力学、超微结构和免疫组织化学方法的研究进展 关于确定正常和非正常情况下流动阻力轨迹的探讨 青光眼已经成为一种现实的可能性。新组织学 探针(免疫亲和标记和荧光物理化学探针)， 结合强大的新形态方法(快速冷冻/深度冷冻 Etch)将允许我们以一种不同的方式可视化流出路径 以前是可能的，因此允许我们极大地改进我们的模型 含水流出的流体力学。反过来，模特们已经并将会 继续指导这些形态研究的性质，通过 表明进一步调查的最佳方向是什么。

Our broad goal is to determine the principal site of resistance to the outflow of aqueous humor from the normal eye, and to determine how resistance is changed in primary open-angle glaucoma (POAG). We have recently identified several new fundamental features of the aqueous outflow system that appear to have important hydrodynamic implications. Among these is a previously unrecognized hydrodynamic interaction, the "funneling" effect, between the pores of the inner wall endothelium of Schlemm's canal and the juxtacanalicular connective tissue (JCT), that may greatly increase the flow resistance of this region. We plan to determine the importance of this phenomenon by combining perfusion studies, morphometric examination of the region where the "funneling" effect is manifest, and engineering porous media analysis. A further finding of our group is that much of the protein in the aqueous humor enters via the root of the iris rather than, as conventionally thought, through the posterior chamber. The immediate proximity of this protein entry point to the trabecular meshwork (TM) raises the possibility that the concentration of protein within the inter-trabecular spaces may be much higher than previously suspected. Initial experimental studies in bovine eyes have demonstrated the hydrodynamic implications of this added protein load, and suggest that these proteins may contribute to the normal maintenance of bovine outflow resistance. The decrease in outflow resistance that occurs in non-human experimental perfusions ("wash-out") can now be explained and prevented. We plan to explore this finding in greater depth and to determine its relevance to human outflow physiology. Finally, as occurs in other connective tissues, we have demonstrated an age-related decrease of glycosaminoglycans in the TM, and postulate that this decrease may have important physicochemical hydrodynamic consequences including an increased tissue surface hydrophobicity perhaps leading to coalescence of collagen fibrils and adsorption of lipophilic proteins. Using morphological techniques, including fluorescent, hydrophobic probes, we will determine the extent of these changes in POAG; and, we will experimentally modify the aqueous outflow pathway to simulate these changes and determine their effect on aqueous outflow dynamics. Exploiting our combined expertise in the areas of modeling, hydrodynamics, ultrastructural and immunohistochemical methods, progress toward determining the locus of flow resistance in normal and glaucomatous eyes has become a realistic possibility. New histological probes (immunoaffinity markers and fluorescent physicochemical probes), in conjunction with powerful new morphological methods (quick freeze/deep etch) will allow us to visualize the outflow pathway in ways not previously possible, thus allowing us to greatly refine our models of the hydrodynamics of aqueous outflow. In turn, the models have and will continue to direct the nature of these morphological studies by suggesting where further investigation is best directed.