# Modulation of Outflow Facility and Biomechanics

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $390,000

## Abstract

PROJECT SUMMARY
Primary open angle glaucoma (POAG) is a leading cause of irreversible blindness, and elevated intraocular
pressure (IOP) is the primary risk factor. By 2040, it is predicted that 112 million people worldwide will have
glaucoma. The IOP is maintained through a dynamic balance between the production and drainage of the
aqueous humor primarily via the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and
Schlemm's canal (SC) endothelium of the conventional outflow pathway. Outflow tissues are hyperviscoelastic
(large-deformation and pressure-dependent) and dynamically interact with aqueous humor through an active,
two-way, fluid-structure interaction coupling. While glaucoma affects the morphology and mechanical properties
of the outflow tissues, the biomechanical and hydrodynamics states in glaucoma eyes are still largely unknown.
Assessment of the dynamic biomechanical properties of the TM, JCT, and inner wall endothelial cells of SC with
their basement membrane tissues in normal and disease will improve our understanding of the mechanisms of
IOP regulation and the dynamic outflow resistance and could be a target for new diagnostic and therapeutic
biomarkers in glaucoma. The goal of this project is to assess the biomechanical and hydrodynamic effects
of different drugs and treatments on outflow facility modulation through an inverse finite element method
coupled with an optimization algorithm and advanced OCT imaging data. In this project, the low-flow (LF)
and high-flow (HF) regions in human donor eyes will be determined by confocal imaging of the FluoSpheres in
the outflow pathway. Two-photon excitation microscopy will be used to measure the velocity of microbeads in
the TM while the SC is negatively pressurized. The TM/JCT/SC complex in the LF and HF regions will be
dissected and subject to tensile loading until failure. The elastic moduli of the normal and glaucomatous human
donor eyes in the LF and HF regions will be calculated. A quadrant of the anterior segment from normal and
glaucomatous human donor eyes in LF and HF regions will be positively and negatively pressurized and imaged
using a visible-light green OCT. The TM, JCT, SC inner wall boundaries in a course of dynamic motion will be
segmented using a deep neural network algorithm to reconstruct a finite element mesh of the TM, with the
adjacent JCT and the SC inner wall. A mesh-free, beam-in-solid material-modeling algorithm will be used to
distribute the collagen fibrils into the ECM of the TM and JCT. An inverse finite element method will be coupled
with an optimization algorithm to characterize the ECM/collagen fibrils hyperviscoelastic mechanical properties
in the LF and HF regions such that the TM, JCT, SC inner wall dynamic motion and OCT imaging data best
match over time. 3D finite element model of the TM/JCT/SC complex will be reconstructed using the OCT images
and will be subject to aqueous humor pressure elevation using fluid-structure inte...

## Key facts

- **NIH application ID:** 10856829
- **Project number:** 1R01EY036011-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Alireza Karimi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856829

## Citation

> US National Institutes of Health, RePORTER application 10856829, Modulation of Outflow Facility and Biomechanics (1R01EY036011-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10856829. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*