(360e) Effects of Porous Connective Tissue Heterogeneity on Aqueous Humor Outflow

Aqueous humor (AH), necessary for nourishment of clear, avascular structures, is secreted by the ciliary processes in the posterior chamber of the eye largely independent of intraocular pressure (IOP). The bulk of AH drainage is through the conventional outflow pathway where it must flow through the juxtacanalicular tissue (JCT) and the inner wall (IW) endothelium of Schlemm's canal (among other tissues and structures). Because this route is pressure dependent and AH is secreted largely independent of pressure, increased flow resistance in this region causes elevated IOP, which is the major risk factor of glaucoma. There have been many efforts to quantify the resistance of various parts of the conventional outflow pathway and identify the site(s) of major resistance. However, the site(s) of major resistance in this pathway is largely unknown for both glaucomatous and non-glaucomatous eyes. The major source of resistance in the conventional outflow pathway is believed to be caused by a coupling between the JCT and the IW.

Previous studies of the JCT have used Darcy's law to model flow in this porous connective tissue. They have all treated it as a homogeneous tissue (i.e. constant permeability) and underestimated the overall resistance seen even in eyes with normal IOP. The IW is continuous endothelial lining with micron sized pores. The combination of pores and essentially impermeable endothelial cells produces a funneling effect in the JCT increasing its apparent resistance. Previous studies concluded this funneling effect should increase the resistance of the JCT 30 fold. This study uses a three dimensional Galerkin finite element method with highly variable permeability to model flow in the JCT using Darcy's Law. A thin layer of elements is added to the outflow surface of the JCT mesh to simulate the IW. The pore structure of the IW is modeled by assigning periodically spaced elements with high permeability (open pores) and the rest with low permeability (essentially impermeable endothelial cells). The finite element method is used because it provides a straightforward technique for approximating the solution to the PDE, varying permeability, and enforcing boundary conditions. An algebraic multigrid iterative solver is used to solve the resultant linear system to provide computational efficiency allowing a sub-micron resolution.

The resistance of the JCT without effects from the IW is 35 ? 68% greater for a heterogeneous tissue as opposed to a homogeneous. When the IW is introduced into the domain, the resistance is increased 3-9 fold for a homogeneous JCT and 18-19 fold for a heterogeneous JCT. Because cellular and extracellular structures in the JCT become denser proximal to the IW endothelium, resistance to AH outflow in this region of the tissue and funneling effects created by pores of the IW become amplified. Recent studies have showed that the pore density of the IW is actually 90-95% less than previously believed. Simulations with a pore density 7.5% of its previous value further increase the resistance another 13-17 fold for a heterogeneous JCT.