# Caveolae-Based Mechanosensors for Conventional Outflow Regulation

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $615,972

## Abstract

Project summary
Glaucoma is the second leading cause of blindness worldwide with primary open angle glaucoma (POAG)
being the most prevalent form. The primary risk factor for POAG, elevated intraocular pressure (IOP), results
from pathology in the conventional outflow pathway. The IOP-dependent mechanical responsiveness of the
conventional outflow tissue is critical to the homeostatic maintenance of IOP in the normal range, however, the
mechanosensors and their transduction pathways, are not well-understood. In this project, we will examine one
mechanical sensor, caveolae, which we have found to play important roles in outflow cell contractile
processes. Gene variants at the CAV1/2 genes, which encode the essential proteins for caveolae formation,
reproducibly associate with POAG and, importantly, with IOP elevation. Ablation of CAV1 both globally and in
outflow cell-specific contexts results in ocular hypertension and defects in aqueous humor drainage from the
conventional outflow pathway. The cell-intrinsic mechanisms by which caveolae transduce responses to IOP
fluctuations and the connection between CAV1/2 gene variants not understood and this project expands on our
prior work to address these gaps in our understanding. We hypothesize that outflow pathway caveolae are
mechanosensitive/mechanoprotective platforms that transduce changes in IOP in the trabecular meshwork, the
Schlemm’s canal, and in the distal outlow pathway vasculature to dynamically regulate aqueous humor
drainage and thereby modulate IOP. We also predict that POAG-associated CAV1/2 risk variants impact the
mechanically-induced transcriptional program to build caveolae. The successful completion of these studies
has clear

## Key facts

- **NIH application ID:** 10801453
- **Project number:** 2R01EY028608-05
- **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:** 2024
- **Award amount:** $615,972
- **Award type:** 2
- **Project period:** 2018-09-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801453

## Citation

> US National Institutes of Health, RePORTER application 10801453, Caveolae-Based Mechanosensors for Conventional Outflow Regulation (2R01EY028608-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10801453. Licensed CC0.

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