# Exosomes and Conventional Outflow Homeostasis

> **NIH NIH R00** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $249,000

## Abstract

Project Summary
Glaucoma is an optic neuropathy in which the primary risk factor is elevated intraocular pressure (IOP).
Dysregulation of conventional outflow homeostasis results in elevated IOP. Key elements of outflow homeostasis
are the turnover of extracellular matrix (ECM), which also determines preferential flow passageways through the
tissue. In fact, there is recent evidence of differential ECM gene expression between regions of low and high
flow in the trabecular meshvvork (TM). In cancer, dysregulation of ECM homeostasis has been demonstrated to
involve extracellular nanovesicles, known as exosomes. Exosome release is tightly regulated, and they are
differentiated from other nanovesicles based on their size, cell type-specific function and cargo. Amongst others,
their functions include waste management, cell-cell signaling and ECM turnover. As a result, we hypothesize
that exosomes released from TM cells play a role in opsonizing ECM in the outflow pathway, contributing
to segmental flow, and altered ECM homeostasis in glaucoma. This study aims to investigate the role of
exosomes in regulating ECM by human TM cells and in TM tissues. During the independent phase, I will examine
how IOP effects exosome release and regulation in the conventional outflow pathway in terms of segmental flow.
Next, using human TM cells and TM tissues, I will investigate how exosomes can be used to ameliorate a
glaucoma phenotype and ocular hypertension. As outcomes of this research we expect to (i) identify a role for
exosomes in segmental flow (ii) determine the effect of IOP on exosome release and function (iii) identify ECM
targets for exosome regulation and, (iv) ascertain if exosomes can be used to normalize ECM homeostasis.

## Key facts

- **NIH application ID:** 10751049
- **Project number:** 5R00EY031737-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Fiona McDonnell
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2023-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751049

## Citation

> US National Institutes of Health, RePORTER application 10751049, Exosomes and Conventional Outflow Homeostasis (5R00EY031737-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10751049. Licensed CC0.

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