The Effect of Intraocular Pressure Load Boundary on the Biomechanics of the Human Conventional Aqueous Outflow Pathway

Abstract

Background: Aqueous humor outflow resistance in the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm’s canal (SC) endothelium of the conventional outflow pathway actively contribute to intraocular pressure (IOP) regulation. Outflow resistance is actively affected by the dynamic outflow pressure gradient across the TM, JCT, and SC inner wall tissues. The resistance effect implies the presence of a fluid–structure interaction (FSI) coupling between the outflow tissues and the aqueous humor. However, the biomechanical interactions between viscoelastic outflow tissues and aqueous humor dynamics are largely unknown. Methods: A 3D microstructural finite element (FE) model of a healthy human eye TM/JCT/SC complex was constructed with elastic and viscoelastic material properties for the bulk extracellular matrix and embedded elastic cable elements. The FE models were subjected to both idealized and a physiologic IOP load boundary using the FSI method. Results: The elastic material model for both the idealized and physiologic IOP load boundary at equal IOPs showed similar stresses and strains in the outflow tissues as well as pressure in the aqueous humor. However, outflow tissues with viscoelastic material properties were sensitive to the IOP load rate, resulting in different mechanical and hydrodynamic responses in the tissues and aqueous humor. Conclusions: Transient IOP fluctuations may cause a relatively large IOP difference of ~20 mmHg in a very short time frame of ~0.1 s, resulting in a rate stiffening in the outflow tissues. Rate stiffening reduces strains and causes a rate-dependent pressure gradient across the outflow tissues. Thus, the results suggest it is necessary to use a viscoelastic material model in outflow tissues that includes the important role of IOP load rate.

The role of conventional and unconventional adaptive routes in lowering of intraocular pressure: Theoretical model and simulation

“… 12 Relation (20a) is a nonlinear Ohm's law representing the hydraulic component of the UncAR, while relation (20c) is a nonlinear drug-controlled current source representing the mechanochemical component of the UncAR. 25 In the case of (20a) , we see that if w ( x ) is negative, then , in agreement with the physical consideration that no hydraulic AR is expected if the pressure is below its baseline value. In the case of (20c) , we see that arbitrary increasing drug concentration does not significantly improve the efficacy of the mechanochemical AR (saturation effect).…”

Modeling the Endothelial Glycocalyx Layer in the Human Conventional Aqueous Outflow Pathway

“…While we are not aware of any experimental studies that have calculated the role of the glycocalyx layer in the resultant outflow resistance and aqueous humor hydrodynamics across the outflow pathway, numerical methods, such as the EFSI, may help to expand our knowledge of glycocalyx biomechanics. In this study, a 3D FE model of the human TM/JCT/SC complex was constructed [ 49 , 50 ] ( Figure 1 ) and subjected to an aqueous humor inflow of 0 to 15 mmHg. The outflow tissues were covered with a thin electric double layer (~109 nm [ 19 ]) to represent the endothelial glycocalyx layer [ 51 ].…”

“…The 3D FE model of the TM/JCT/SC complex of a normal human donor of European descent was constructed [ 52 ]. The descriptions in regard to the imaging, segmentation, and volume meshing of the TM/JCT/SC complex FE model were fully explained in our prior publications [ 46 , 47 , 49 , 50 , 53 ].…”

“…Element quality assessment and time-step analysis were carried out using LS-DYNA (Ansys/LS-DYNA, Pennsylvania, US) [ 48 , 54 , 60 , 61 , 62 ]. Mesh density analyses were conducted for the FE model as described in our previous publications [ 46 , 47 , 49 , 50 ]. To have a fully unbiased analysis, the structure, density, and distribution of the mesh in the models were the same.…”

“…In prior studies, our group has calculated the elastic and viscoelastic biomechanical properties of the healthy and glaucomatous human outflow tissues using dynamic SC pressurization, high-resolution optical coherence tomography (OCT), and finite element method coupled with an optimization algorithm [ 46 , 47 , 48 ]. Through an active, two-way, fluid–structure interaction of the outflow tissues and aqueous humor dynamics, we studied the hydrodynamics of the aqueous humor across the healthy and glaucomatous outflow pathways [ 49 , 50 ]. While we have studied the biomechanics of the human aqueous outflow pathway using experimental and computational techniques, the important role of the glycocalyx layer in the resultant outflow resistance across the outflow pathway has not been fully explored.…”