# Impact of Menopause on the Aqueous Outflow Pathway

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2021 · $158,498

## Abstract

Project Summary/Abstract
Glaucoma is the leading cause of irreversible blindness and is projected to affect 112 million people worldwide
by 2040. Women represent 59% of the glaucoma population, highlighting the need to understand if there are
sex-specific risk factors for glaucoma. For example, early menopause increases the risk of developing glaucoma.
Estrogen receptor polymorphisms in women are associated with ocular hypertension (an important causal risk
factor for glaucoma). Moreover, menopause causes a 1-3 mmHg increase in intraocular pressure (IOP), while
hormone therapy containing estrogen reduces IOP. These data suggest that the age of menopause, menopause
and estrogen levels influence glaucoma risk or IOP, but the mechanism(s) is unknown.
IOP is affected by many factors, but aqueous outflow resistance is the key determinant, which is primarily
controlled by trabecular meshwork (TM) function. Outflow resistance is segmental with high and low flow regions,
and segmental flow correlates with TM stiffness. Notably, menopause and estrogen levels affect the stiffness of
many tissues, suggesting a possible mechanism by which altered estrogen levels affect IOP. These changes in
segmental flow may be related to altered protein expression since menopause alters protein levels known to
influence aqueous outflow resistance. Thus, it is hypothesized that menopause increases IOP by increasing
aqueous outflow resistance through stiffening the TM in high and low flow regions, thus increasing a
woman’s risk of developing glaucoma. This proposal addresses the hypothesis in an animal model of
menopause by measuring IOP and aqueous outflow resistance (Aim 1), and regional TM stiffness using Atomic
Force Microscopy (Aim 2).
This proposal achieves these aims using several approaches: Experiment A employs a well-established model
of menopause, ovariectomy (OVX), in young (age 3-4 months) and middle-aged (age 9-10 months) female
Brown Norway rats, and physiological menopause in elderly female rats (age 18-19 months). Experiment B will
determine if topical estrogen therapy mitigates the effects of menopause, and investigates if this therapy affects
IOP, outflow resistance, and TM stiffness in elderly male rats (age 18-19 months). In all animals, IOP will be
measured using rebound tonometry for 8 weeks, followed by measurement of outflow resistance (via iPerfusion)
and regional TM stiffness (via atomic force microscopy) in one eye. Contralateral eyes will be used to assess:
estrogen levels or structure and composition along the outflow pathway. Preliminary data support this hypothesis,
showing that IOP and aqueous outflow resistance are increased after OVX. This proposal will build on these
data and expects to demonstrate that menopause increases TM stiffness and that topical estrogen therapy
prevents these changes. These findings will provide functional and mechanistic insight into the association
between menopause and glaucoma, and the benefits of topical estro...

## Key facts

- **NIH application ID:** 10222707
- **Project number:** 5R01EY030871-02
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Andrew J Feola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $158,498
- **Award type:** 5
- **Project period:** 2020-08-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222707

## Citation

> US National Institutes of Health, RePORTER application 10222707, Impact of Menopause on the Aqueous Outflow Pathway (5R01EY030871-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10222707. Licensed CC0.

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