# Exosomes and Conventional Outflow Homeostasis

> **NIH NIH K99** · DUKE UNIVERSITY · 2020 · $122,823

## 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 meshwork (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 mentored
phase, I will first examine the effect of mechanical stretch on exosomes released from primary human TM cells
and create a comprehensive profile of exosomes released from TM explants, specifically profiling regions of low
and high flow. During the independent phase, I will examine how IOP effects exosome release and regulation in
the conventional outflow pathway in terms of segmental flow before examining how exosomes may be used as
a platform to ameliorate the dysfunctional ECM homeostasis in glaucoma. 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:** 10039561
- **Project number:** 1K99EY031737-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Fiona McDonnell
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,823
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039561

## Citation

> US National Institutes of Health, RePORTER application 10039561, Exosomes and Conventional Outflow Homeostasis (1K99EY031737-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10039561. Licensed CC0.

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