# In vivo trabecular meshwork gene expression response to elevated IOP

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $186,725

## Abstract

Project Summary
Elevated intraocular pressure (IOP) is a primary risk factor for glaucoma and lowering IOP is the only effective
clinical strategy to slow glaucomatous vision loss. IOP is regulated by the trabecular meshwork (TM), which
builds a resistance to aqueous humor outflow. Previous studies using an ex vivo organ culture model showed
that a 6-8 hour sustained pressure elevation induces IOP homeostasis, where the resistance is remodeled to
facilitate aqueous outflow and alleviate IOP. This involves many up- and down-regulated genes. Upon IOP
lowering, these `homeostatic' genes should theoretically recover to normal expression levels within 24-48 hours,
but this has not yet been investigated. These events have only been studied in ex vivo organ cultures, which
lack a normal diurnal IOP fluctuation, episcleral venous pressure and ongoing aqueous humor formation. Better
understanding of this homeostatic response requires studying in vivo TM gene expression changes in response
to a controlled IOP challenge. Various in vivo rodent IOP models exist, but the technical methods used to create
pressure elevation compromises TM cell function and causes unpredictable spikes in IOP. The Controlled
Elevation of IOP (CEI) rat model is ideal to study these in vivo TM gene expression changes. Here, a cannula is
placed into the anterior chamber, anterior to the iris, and sterile balance salt solution is delivered to elevate
pressure. A defined IOP elevation of known duration can thus be applied to the eye. Importantly, since the angle
is open, IOP elevation produces stretching/distortion of the TM mimicking that found in glaucoma patients. This
allows us, for the first time, to study in vivo IOP-related gene expression changes in the TM. In this study, we will
use RNA-seq to identify TM genes altered in response to, and recovery from, a single IOP exposure. We
hypothesize that TM gene expression changes following the in vivo CEI will identify novel pathways related to
IOP homeostasis. In SA#1, CEI will be performed where eyes are subjected to a 50 mmHg pressure elevation
for 8 hours (CEI 50). Controls will include eyes from animals exposed to 20 mmHg for 8 hours (CEI 20) and
naïve animals, without anesthetic or surgical manipulations. Immediately following CEI (0 hours), RNA will be
isolated from TM tissue and RNA-seq will be performed. Biostatistical analyses will determine significantly up-
and down-regulated IOP-related genes in vivo. In SA#2, CEI 50 and CEI 20 will be performed, but rats will be
allowed to recover for 24 or 48 hours. RNA-seq samples will be run concomitant with samples from SA#1 to
allow us to rigorously compare CEI 50 and control groups at all time points (0, 24, 48 hours). These analyses
will enable us to separate IOP homeostatic genes (those that recover in 24-48 hours) from non-homeostatic
genes (genes that display a prolonged response). Together, results from this study will provide a comprehensive
identification of the TM gene pro...

## Key facts

- **NIH application ID:** 10487567
- **Project number:** 5R21EY033073-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Kate E Keller
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $186,725
- **Award type:** 5
- **Project period:** 2021-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487567

## Citation

> US National Institutes of Health, RePORTER application 10487567, In vivo trabecular meshwork gene expression response to elevated IOP (5R21EY033073-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10487567. Licensed CC0.

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