HYDRODYNAMICS OF AQUEOUS HUMOR OUTFLOW

描述(申请人提供)：青光眼是美国导致失明的主要原因之一，它与眼内压升高有关，这是由于眼内房水排出时对房水流动的阻力增加所致。然而，这种增加的流动阻力的来源尚未确定。我们的总体目标是确定(I)正常眼睛的流动阻力是如何产生的，(Ii)这种流动阻力是如何调节的，以及(Iii)是什么导致青光眼中这种流动阻力的增加。 传统上认为，紧邻Schlemm管下方的跟侧旁组织(JCT)负责正常眼的大部分流出阻力，该区域细胞外基质的变化导致青光眼。我们的团队现在已经证明，使用一种被称为快速冷冻/深度蚀刻的形态技术可视化的JCT，不能产生显著的流出阻力，至少在正常的人眼中是这样。这是一个重要的结论，我们建议继续使用这项技术来检查青光眼。 形成Schlemm管内壁的内皮细胞被广泛认为只产生一小部分流出阻力，这是基于对内壁内皮孔的流体动力学评估。然而，我们最近证明，青光眼的毛孔密度比正常眼小，可能低五倍。这表明青光眼的血流阻力升高可能是由于形成这些内皮孔的能力降低所致。我们将在拟议的研究中研究这一可能性。如果得到证实，这些发现可能最终让我们找到青光眼特有的高眼压的最终原因。

DESCRIPTION (provided by applicant): Glaucoma, a leading cause of blindness in the United States, is associated with an increased intraocular pressure (IOP) that results from an increased resistance to the flow of aqueous humor as it drains from the eye. However, the source of this increased flow resistance has not been determined. Our overall goals are to determine (i) how flow resistance is generated in the normal eye, (ii) how this flow resistance is modulated and (iii) what causes this flow resistance to increase in glaucoma. It is conventionally believed that the juxtacanalicular tissue (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 in this region lead to glaucoma. Our group has now shown that the JCT, as visualized using a morphological technique known as quick-freeze/deep-etch, cannot generate a significant fraction of outflow resistance, at least in the normal human eye. This is an important conclusion, and we propose to continue to use this technique to examine the glaucomatous eye. The endothelium forming the inner wall of Schlemm's canal is widely thought to generate only a small fraction of outflow resistance, based on a hydrodynamic assessment of endothelial pores in the inner wall. However, we have recently demonstrated that the pore density in glaucomatous eyes is less than that found in normal eyes, perhaps as much as five-fold less. This suggests that the elevated flow resistance of glaucomatous eyes may be due to a decreased capacity to form these endothelial pores. We will examine this possibility in our proposed studies. If confirmed, these findings may finally allow us to find the ultimate cause of the elevated IOP characteristic of glaucoma.