HYDRODYNAMICS OF AQUEOUS HUMOR OUTFLOW

描述（由申请人提供）：青光眼是美国致盲的主要原因，与眼内压（IOP）升高有关，眼内压升高是由于眼房水从眼睛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）正常眼睛中如何产生流动阻力，（ii）如何调节这种流动阻力以及（iii）是什么导致青光眼中这种流动阻力增加。 传统上认为，紧邻施累姆氏管下方的睫状小管组织（JCT）是正常眼中大部分流出阻力的原因，并且该区域中细胞外基质的变化导致青光眼。我们的研究小组现在已经表明，JCT，作为可视化使用的形态学技术称为速冻/深蚀刻，不能产生一个显着的部分流出阻力，至少在正常的人眼。这是一个重要的结论，我们建议继续使用这项技术来检查眼昏迷。 基于对内壁中内皮孔的流体动力学评估，形成Schlemm管内壁的内皮被广泛认为仅产生一小部分流出阻力。然而，我们最近发现，青光眼眼的孔密度比正常眼的孔密度低，可能低5倍，这表明青光眼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。我们将在拟议的研究中探讨这种可能性。如果得到证实，这些发现可能最终使我们能够找到青光眼特征性IOP升高的最终原因。

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.