HYDRODYNAMICS OF AQUEOUS HUMOR OUTFLOW

我们的主要目标是确定抵抗的主要地点， 流出的水状体从正常的眼睛，并确定如何 在原发性开角型青光眼（POAG）中阻力改变。 我们有 最近确定了几个新的基本特征的水 外流系统，似乎有重要的水动力影响。 其中有一种以前未被认识到的流体动力学相互作用， “漏斗”效应，在血管内皮细胞的孔之间， Schlemm管和小管结缔组织（JCT）， 可能大大增加该区域的流动阻力。 我们计划 通过结合灌注来确定这种现象的重要性， 研究，对“漏斗”区域的形态测量学检查 效果明显，可用于工程多孔介质分析。 我们小组的进一步发现是， 幽默通过虹膜根部进入，而不是像传统的那样， 我想，通过后房。 这种直接接近 小梁网的蛋白质进入点（TM）提高了 小梁间的蛋白质浓度 空间可能比以前怀疑的要高得多。 初始 在牛眼中的实验研究已经证明了流体动力学 这种增加的蛋白质负荷的影响，并表明这些蛋白质 可能有助于牛流出阻力的正常维持。 在非人类实验中发生的流出阻力的降低 现在可以解释和防止灌注（“洗出”）。 我们计划 更深入地探讨这一发现，并确定其相关性， 人体外流生理学 最后，与其他结缔组织一样，我们已经证明了 TM中糖胺聚糖的年龄相关性减少，并假设 这种减少可能具有重要的物理化学流体动力学 可能包括组织表面疏水性增加的后果 导致胶原纤维的聚结和亲脂性 proteins. 使用形态学技术，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流出途径， 模拟这些变化并确定它们对水流出影响 动力学 利用我们在建模领域的综合专业知识， 流体力学，超微结构和免疫组织化学方法，进展 为了确定正常情况下的流阻轨迹， 昏迷的眼睛已经成为一个现实的可能性。 新组织学 探针（免疫亲和标记和荧光物理化学探针）， 结合强大的新形态学方法（快速冷冻/深度 蚀刻）将使我们能够可视化流出途径的方式， 以前可能的，从而使我们能够大大完善我们的模型， 水外流的流体动力学。 反过来，这些模型已经并将 继续指导这些形态学研究的性质， 这表明了进一步调查的最佳方向。

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.