HYDRODYNAMICS OF AQUEOUS HUMOR OUTFLOW

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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.