# Effects of estrogen on trabecular meshwork regulation of intraocular pressure

> **NIH NIH F31** · AUGUSTA UNIVERSITY · 2020 · $39,868

## Abstract

PROJECT SUMMARY
The goal of this project is to characterize the effects of estrogen and its receptor - estrogen receptor 1 (ESR1)
- on aqueous humor outflow, intraocular pressure, and risk for glaucoma development. Primary open-angle
glaucoma (POAG), as the most common subtype of glaucoma, is characterized by retinal ganglion cell death,
optic nerve degeneration, and progressive visual field loss without an identifiable cause. Elevated intraocular
pressure (IOP) is the primary and only modifiable risk factor for POAG development. This pressure is
regulated by the trabecular meshwork (TM) which modulates aqueous humor (AH) outflow. Previously,
genome-wide association studies identified >122 IOP-associated genes. Our integrated bioinformatics
analysis revealed that ESR1, also known as estrogen receptor α, was at the center of a functional network of
these IOP-associated genes, suggesting that it may play a role in IOP regulation. Several epidemiological
studies have suggested that low estrogen levels may contribute to glaucoma risk due to a higher prevalence
of POAG in males than females and a higher prevalence in post-menopausal females than pre-menopausal
females or post-menopausal females undergoing hormone replacement therapy. Inversely, pregnancy, a high
estrogen state, has been associated with lower IOP. In addition, it has been well-established that estrogen is
protective for several ocular cell types, including retinal and corneal cells. However, the impact of estrogen
on the TM has yet to be explored. Therefore, in this proposal, we hypothesize that moderate estrogen levels
reduce IOP and POAG risk by promoting proper TM function through ESR1 transcriptional regulation of IOP
and POAG related genes. We will test this hypothesis with the following aims. In Aim 1, in order to assess the
effects of estrogen signaling on IOP and ocular health, we will measure IOP and conduct retinal optical
coherence tomography (OCT) on male and female Esr1-/- mice and wild type female mice undergoing a
bilateral oophorectomy. In Aim 2 we will determine the effects of estradiol, the active form of estrogen, on the
transcriptional profile, morphology, and function of primary human TM cells using RNA-Seq and growth,
contraction, and phagocytic assays. Successful completion of this project will improve our current
understanding of the role of the TM in POAG pathogenesis, confirm low estrogen levels as a novel risk factor
for high tension POAG, and identify novel therapeutic targets for this blinding illness.

## Key facts

- **NIH application ID:** 10068893
- **Project number:** 1F31EY031973-01
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Hannah Abigail Youngblood
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,868
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068893

## Citation

> US National Institutes of Health, RePORTER application 10068893, Effects of estrogen on trabecular meshwork regulation of intraocular pressure (1F31EY031973-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10068893. Licensed CC0.

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