# Mechanisms of Trabecular Meshwork Regeneration by Stem Cells

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2023 · $456,830

## Abstract

Project Summary
Glaucoma is a leading cause of irreversible blindness throughout the world and the second leading cause of
blindness overall in the USA. Elevated intraocular pressure (IOP) and aging are the most important risk factors
for most forms of glaucoma. IOP level is highly dependent on the rate at which the aqueous humor is filtered
through the conventional outflow pathway containing the trabecular meshwork (TM). Reduced cellularity within
the TM and abnormal extracellular matrix (ECM) turnover occur in glaucomatous conditions and correlate with
increased outflow resistance, elevated IOP, and subsequent vision loss. The goal of this project is to define the
mechanisms of stem cell homing and engrafting to the TM tissue, activating regeneration of the TM tissue, and
hence restoring outflow facility, reducing IOP, and preventing vision loss. In our previous funding period, we
have identified the mechanisms of stem cell homing and integration are partially associated with CXCR4/SDF1
chemokine pair and α5β1 integrin. We have also confirmed that TM stem cells (TMSCs), after intracamerally
injection, can regenerate the TM tissue, reduce IOP, and preserve the retinal ganglion cell function in a mouse
glaucoma model. This project is designed to test specific hypotheses about the mechanisms by which human
TMSCs remodel the pathological TM tissue and restore the TM function. Specific Aim 1 tests the hypothesis
that TMSCs and differentiated TM cells remodel the abnormal TM ECM via the COX2/PGE2/MMP pathway.
We will utilize myocilin mutant TM cells and dexamethasone-treated TM cells as well as a mouse glaucoma
model with myocilin mutation to test how TMSCs promote the ECM turnover and modify the TM segmental
outflow pattern. Specific Aim 2 tests the hypothesis that transplanted TMSCs can promote endogenous
TMSC activation, migration, and function via the SOX21/WNT signaling. We will unveil if the endogenous
TMSCs are viable with a reduced number in aged and glaucomatous TM tissue in human and in mice and
uncover how TMSCs awake endogenous TMSCs via SOX21/WNT signaling. The scientific impact of this study
will be the elucidation of the cellular and molecular mechanisms of TM regeneration potential by stem cells.
The results may also directly lead to the design of stem cell-based therapies or adjunctive treatments that
prevent blindness from glaucoma clinically.

## Key facts

- **NIH application ID:** 10895151
- **Project number:** 7R01EY025643-07
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Yiqin Du
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $456,830
- **Award type:** 7
- **Project period:** 2015-09-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895151

## Citation

> US National Institutes of Health, RePORTER application 10895151, Mechanisms of Trabecular Meshwork Regeneration by Stem Cells (7R01EY025643-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10895151. Licensed CC0.

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