# Mechanism of Stem Cell Restoration of IOP Regulation

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $186,725

## Abstract

Project Summary:
Glaucoma is a major blinding disease, with elevated intraocular pressure (IOP) as a crucial risk factor. Although
various medications, stents, lasers, and surgeries are currently used to treat glaucoma patients, some are
invasive, others often exhibit limited effectiveness or become so over time and patient compliance remains a
major issue. The normal trabecular meshwork (TM) facilitates intraocular pressure (IOP) homeostasis, i.e.
responds to pressure disbalances and adjusts the outflow resistance correctively, while the glaucomatous TM
cannot. Glaucomatous eyes also have reduced numbers of TM cells. Our previous work demonstrated that TM
cellularity reduction in a model system compromised IOP homeostatic response. Our long-term goal is to
restore IOP homeostatic capability by transplanting autologous, patient-derived human induced pluripotent stem
cells (iPSCs) or human mesenchymal stem cells (hMSCs) to treat glaucomatous cell loss. Previously we
transplanted either of these two cell types, differentiated to TM-like cells, into TM in a human cell-depletion model
for glaucoma. These differentiated stem cells restored IOP homeostasis by an undetermined mechanism. The
goal of this proposal is to establish what that mechanism is and to evaluate conditions that may optimize
moving eventually toward clinical trials in a new era of regenerative medicine. Our central working hypothesis
is that the transplanted differentiated stem cells integrate into the tissue and are restoring function directly.
Alternative possibilities include the stem cells triggering endogenous TM cell division or that a stem cell-produced
factor is responsible for the effect. In Specific Aim 1, we will determine the mechanism of stem cell restoration
of IOP homeostasis one week after transplantation. We will do this with both TM-like iPSCs and TM-like hMSCs.
In Specific Aim 2, we will extend the studies, focusing on the mechanism(s) found to be important in Aim 1,
to a longer duration and will compare TM-like iPSCs to TM-like hMSCs for efficacy, efficiency and longevity
of IOP homeostatic restoration. In Specific Aim 3, we will determine the relative efficacy of TM-like iPSCs and
TM-like hMSCs in restoring IOP homeostatic capability to glaucomatous anterior segments. Completion of
these studies is a necessary step to inform any future clinical stem cell therapies for glaucomatous IOP
homeostatic restoration.

## Key facts

- **NIH application ID:** 10220983
- **Project number:** 5R21EY031071-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** MARY Jane KELLEY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $186,725
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220983

## Citation

> US National Institutes of Health, RePORTER application 10220983, Mechanism of Stem Cell Restoration of IOP Regulation (5R21EY031071-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10220983. Licensed CC0.

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