High-resolution modeling of aqueous humor dynamics in the conventional outflow pathway of a normal human donor eye

Background and objective: The conventional aqueous outflow pathway, which includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and inner wall endothelium of Schlemm's canal (SC) and its basement membrane, plays a significant role in regulating intraocular pressure (IOP) by controlling aqueous humor outflow resistance. Despite its significance, the biomechanical and hydrodynamic properties of this region remain inadequately understood. Fluid-structure interaction (FSI) and computational fluid dynamics (CFD) modeling using high-resolution microstructural images of the outflow pathway provides a comprehensive method to estimate these properties under varying conditions, offering valuable understandings beyond the capabilities of current imaging techniques.

Methods: In this study, we utilized high-resolution 3D serial block-face scanning electron microscopy (SBF-SEM) to image the TM/JCT/SC complex of a normal human donor eye perfusion-fixed at an IOP of 7 mm Hg. We developed a detailed 3D finite element (FE) model of the pathway using SBF-SEM images to simulate the biomechanical environment. The model included the TM/JCT/SC complex (structure) with interspersed aqueous humor (fluid). We employed a 3D, inverse FE algorithm to calculate the unloaded geometry of the TM/JCT/SC complex and utilized FSI to simulate the pressurization of the complex from 0 to 15 mm Hg.

Results: Our simulations revealed that the resultant velocity distribution in the aqueous humor across the TM/JCT/SC complex is heterogeneous. The JCT and its deepest regions, specifically the basement membrane of the inner wall of SC, exhibited a volumetric average velocity of ∼0.011 mm/s, which is higher than the TM regions, with a volumetric average velocity of ∼0.007 mm/s. Shear stress analysis indicated that the maximum shear stress, based on our FE code criteria, was 0.5 Pa starting from 10 µm into the TM from the anterior chamber and increased to 0.95 Pa in the JCT and its adjacent SC inner wall basement membrane. Also, the tensile stress and strain distributions showed significant variations, with the first principal stress reaching up to 57 Pa (compressive volumetric average) and the first principal strain reaching up to 3.5 % in areas of high mechanical loading. The resultant stresses, strains, and velocities exhibited relatively similar average values across the TM, JCT, and SC regions, primarily due to the uniform elastic moduli assigned to these components. Our computational fluid dynamics (CFD) analysis revealed that while the velocity of the aqueous humor remained consistent, the maximum shear stress was reduced by a factor of thirty.

Conclusion: The uneven distribution of shear stress and velocity within the TM/JCT/SC complex highlights the complex biomechanical environment that regulates aqueous humor outflow.