# Assessing the Impact of Age, Sex, and Menopause on Scleral Biomechanics and Gene Expression

> **NIH NIH R21** · EMORY UNIVERSITY · 2023 · $438,018

## Abstract

Glaucoma is the leading cause of irreversible blindness worldwide and is projected to affect 112 million people
by 2040. Aging is a major risk factor for developing glaucoma. Yet, evidence suggests that the age of menopause
modulates a woman’s risk of developing glaucoma. Overall, women represent 59% of the glaucoma population
highlighting the need to understand the impact of menopause on ocular tissues.
Glaucoma is multifactorial but elevated intraocular pressure (IOP) remains a major risk factor. Elevated IOP
increases optic nerve head (ONH) deformation contributing to the loss of retinal ganglion cells and vision loss in
glaucoma. The extent of ONH deformation is related to IOP and ocular biomechanical properties. Age and
menopause modulate the stiffness of tissues throughout the body and are known to affect gene expression in
the retina. Here, our hypothesis is that menopause will decrease scleral stiffness, exacerbating ONH
deformation thus increasing the risk of developing glaucoma and that these effects are mediated by
altered gene expression profiles in the sclera.
This proposal addresses the hypothesis in a rat model using age and surgical menopause across two integrated
Aims. Aim 1 measures the biphasic mechanical properties of the scleral and Aim 2 assesses gene expression
of the sclera. This proposal achieves these Aims by examining young (3-4 months) and older adult (20-24
months) male and female Long-Evans rats. Young females are divided into pre- and post-menopausal groups.
Menopause will occur by ovariectomy (young) of physiologically (older adults). In our integrated Aims, one eye
is used to assess scleral mechanics while the opposite eye is used to assess gene expression. Age, sex, and
menopause affect multiple gene networks; therefore, we will use RNAseq, an unbiased approach, to examine
gene expression associated with extracellular matrix remodeling. Our preliminary data show that ovariectomy
decreases scleral stiffness, supporting our hypothesis. We also show that age and ovariectomy modulate retinal
gene expression. This proposal provides functional (e.g., scleral mechanics) and mechanistic (e.g., gene
expression) insight into the association between age, sex, menopause, and glaucoma. This proposal will set up
future applications to investigate pathways affected by age and menopause as potential treatments. These
treatments can target mechanical properties or gene expression to decrease the susceptibility to developing
glaucoma.

## Key facts

- **NIH application ID:** 10726826
- **Project number:** 1R21EY035468-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Andrew J Feola
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $438,018
- **Award type:** 1
- **Project period:** 2023-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10726826

## Citation

> US National Institutes of Health, RePORTER application 10726826, Assessing the Impact of Age, Sex, and Menopause on Scleral Biomechanics and Gene Expression (1R21EY035468-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10726826. Licensed CC0.

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