# Estrogen and its Receptor in Intraocular Pressure Regulation

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2023 · $383,430

## Abstract

Abstract
The goal of this application is to determine the role of estrogen and its receptors - estrogen receptor 1 (ESR1)
and G protein coupled estrogen receptor (GPER1) – in regulating intraocular pressure (IOP) through
trabecular meshwork (TM) and Schlemm's canal (SC) endothelial cells. IOP is the primary and only modifiable
risk factor for patients affected with primary open-angle glaucoma (POAG) in the clinic. TM and SC modulate
majority of aqueous humor outflow resistance in the conventional pathway. Despite the significant research
progress in TM/SC outflow dynamics, limited therapeutic targets are available for modulating the conventional
outflow. It is necessary to identify novel targets to lower IOP more efficiently in glaucoma patients with
progressive visual field loss. Several recent genome-wide association studies have identified >150 IOP-
associated genomic loci, which is too many to follow up functionally. Our comprehensive bioinformatics
analyses of these IOP-associated genomic loci indicate the enrichment of ESR1-related gene networks
among these IOP genes. Factors related with menarche, menopause, and oophorectomy have been
associated with POAG. Genetic associations have been identified between sequence variants in estrogen
receptor pathway genes and POAG. Estrogen and ESR1-related pathways including aromatase may affect
the aqueous humor outflow facility and regulate IOP levels. The presence of estradiol in aqueous humor and
ESR1 protein in the TM/SC region further supports the potential role of estrogen and ESR1-related pathways
in IOP regulation. Based on our preliminary data on the elevated IOP levels from mouse models with the loss
of Esr1 or Gper1 as well as their interaction with Nos3, we hypothesize that activation of estrogen signaling
via ESR1 and GPER1 decreases IOP and POAG risk by modulating the turnover of extracellular matrix in the
TM and the NO signaling in the SC. We propose to determine the in vivo effects of loss of estrogen signaling
via Gper1 (Aim 1) or Esr1 (Aim 2) in murine eyes using tissue-specific knockout mice, and to determine the
underlying mechanisms of Gper1 and Esr1-mediated IOP regulation using in vitro primary cell culture models
(Aim3). Successful completion of this project will help reveal the critical role of estrogen signaling in aqueous
outflow pathway and identify novel therapeutic targets to reduce IOP more effectively for this sight-threatening
disease.

## Key facts

- **NIH application ID:** 10595307
- **Project number:** 1R01EY032960-01A1
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Yutao Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $383,430
- **Award type:** 1
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595307

## Citation

> US National Institutes of Health, RePORTER application 10595307, Estrogen and its Receptor in Intraocular Pressure Regulation (1R01EY032960-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10595307. Licensed CC0.

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