# Molecular mechanisms of mechanotransduction in the aqueous outflow pathway

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $369,812

## Abstract

PROJECT SUMMARY/ABSTRACT
There is substantial evidence that pathological increases in intraocular pressure (IOP) play a causal role in the
pathological remodeling of trabecular meshwork cells which regulate the drainage of aqueous humor from the
anterior eye however the identity and function of the mechanosensing mechanisms remains largely unknown.
The present proposal aims to characterize these mechanisms at biophysical, molecular and cellular levels as
well as in bioengineered models of conventional outflow. Aim 1 will establish the mechanical thresholds of
human TM cells obtained from non-symptomatic and glaucomatous patients, characterize effect of mechanical
stress (pressure, stretch and swelling) on intrinsic mechanosensitive channels and establish its time-
dependent properties (acute & chronic adaptation). This is expected to lead to a novel model of tensile
homeostasis in the TM based on balanced activation of opposing types of mechanosensitive channels. Aim 2
links pressure-sensitive channels to the remodeling of actin cytoskeleton and focal adhesion contacts with the
extracellular matrix, uses innovative strain-sensitive optical cytoskeleton probes and defines the function of
mechanical coupling in the regulation of the conventional outflow resistance using biomimetic nanoscaffolds
populated with healthy and glaucomatous human TM cells. The proposed research thus aims to establish
novel conceptual, experimental and translational frameworks that will unify our understanding of retinal IOP
regulation within the context of mechanotransduction, cell swelling, volume sensing and calcium homeostasis,
with the aim to lead towards the development of effective, first-in-kind treatments for glaucoma.

## Key facts

- **NIH application ID:** 10133080
- **Project number:** 5R01EY027920-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** DAVID KRIZAJ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $369,812
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133080

## Citation

> US National Institutes of Health, RePORTER application 10133080, Molecular mechanisms of mechanotransduction in the aqueous outflow pathway (5R01EY027920-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133080. Licensed CC0.

---

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