# Caveolae-based mechanosensors for conventional outflow regulation

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $486,926

## Abstract

Project summary
Glaucoma is the second leading cause of blindness worldwide with primary open angle glaucoma (POAG)
being the most prevalent form. In POAG, elevated intraocular pressure (IOP) is a primary risk factor for the
neurodegenerative changes causing vision loss, and pathology in the conventional outflow pathway is
responsible for elevated IOP. While the molecular mechanisms that control conventional outflow are not well
understood, homeostatic responses of conventional outflow cells to mechanical stimulation have been shown
important. Polymorphisms in the CAV1/2 genes, which encode essential proteins for a putative membrane
mechanical sensor, caveolae, reproducibly associate with POAG and elevated IOP. Genetic deletion of CAV1
in mice ablates caveolae, resulting in ocular hypertension due to functional defects in conventional outflow
function. The mechanism for this defect and the connection between disease-associated polymorphisms and
caveolae function are not understood. This project addresses this important gap in knowledge. Since
mechanical stimulation of human conventional outflow cells induces caveolae disassembly, and caveolae
deficiency renders the conventional outflow pathway more sensitive to IOP induced injury, We hypothesize that
outflow pathway caveolae are mechanosensitive/mechanoprotective platforms that transduce changes in IOP
to enhance outflow by orchestrating both rapid and long-term, adaptive cellular responses. In aim 1 we will test
the hypothesis that caveolae are mechanosensors in the Schlemm’s canal that acutely modulate IOP and
conventional outflow. In aim 2, we will test the hypothesis that caveolae are mechanosensors in the trabecular
meshwork that acutely modulate IOP and conventional outflow. In the final aim, we will test the hypothesis that
caveolae mediate adaptive mechanically-induced transcriptional responses in outflow pathway cells. The
studies have clear

## Key facts

- **NIH application ID:** 9965934
- **Project number:** 5R01EY028608-03
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** MICHAEL H ELLIOTT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $486,926
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965934

## Citation

> US National Institutes of Health, RePORTER application 9965934, Caveolae-based mechanosensors for conventional outflow regulation (5R01EY028608-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9965934. Licensed CC0.

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