IOP-induced Changes in Schlemm’s Canal Dimensions and the Relation to Shear Stress

Abstract

Purpose : In vascular endothelia including Schlemm's canal (SC), nitric oxide (NO) is produced by endothelial NO synthase (eNOS), whose activity and abundance are regulated by shear stress. In simplified elliptical models of SC, wall shear stress (WSS) at elevated intraocular pressures (IOP) is calculated to be comparable to those in large arteries. Using spectral-domain optical coherence tomography (OCT) imaging of living mice, we create more realistic 3D models of SC to estimate WSS and thus investigate the relationship between IOP and shear stress.

Methods : IOP was controlled by intracameral cannulation of anesthetized (ketamine/xylazine, intraperitoneal injection) C57BL/6 mice (6 months old), while simultaneously imaging iridocorneal angle structures using OCT (Envisu R2200, 2 µm resolution, Bioptogen, Inc). Incremental sagittal OCT sections along a 0.2 mm length of SC were acquired at two IOPs (10 and 15 mmHg), to create a stack of images (0.0085 mm distance between image slices). Customized software (Matlab) was used to segment SC on each OCT image, which was easily visualized at the two selected IOPs. A 3D SC replica consisting of SC and 2 collector channels was built using Aviso (FEI) and ANSYS software (ANSYS, Inc.).

Results : When changing IOP in living mice from 10 to 15 mmHg the SC lumen imaged by OCT reduced by 43% on average from an integrated volume of 13.8 ± 5.8 µm³ to 7.8 ± 4.8 µm³. This corresponds to a decrease in SC height from 6.7 µm to 3.8 µm based on previous elliptical models.

Conclusions : IOP elevation from 10 to 15 mmHg decreases SC volume, corresponding to a pressure-dependent decrease in SC height (inner-outer wall separation). Previous elliptical models suggest that this change will lead to an increase in shear stress to levels capable of increasing eNOS activity (~2 dynes/cm²). In conjunction with computational fluid dynamics, our new 3D model of SC at both 10 and 15 mmHg will enable analysis of the fluid flow and estimation of wall shear stress in Schlemm’s Canal.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.