# The Effect of Estrogen Deficiencies on Vision Loss in Glaucoma

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2023 · —

## Abstract

Glaucoma is the largest cause of irreversible blindness in the world and is characterized by the loss of retinal
ganglion cells (RGCs), which transmit visual information from the eye to the brain. While the exact cause of
glaucoma is unknown, recent evidence has shown that early menopause in women is linked with developing
glaucoma. Further, mutations in estrogen receptors and polymorphisms in the estrogen metabolic pathway are
linked with glaucoma in both genders. However, since the number of woman veterans has nearly doubled in
the last ten years, the VA recently formed the Women’s Veterans Health Research Network (WVHRN) to help
focus attention on research and treatments for this increasing population in the veteran population. These data
highlight that estrogen plays a vital role in the development of glaucoma and is an important issue in the VA;
however, the mechanism(s) underlying estrogen’s effects are unknown. We hypothesize that an estrogen
deficiency contributes to the etiology of glaucoma by altering ocular biomechanics, increasing an
individual’s risk for developing glaucoma. In this study, we will investigate the link between estrogen and
glaucoma through three Specific Aims. In our first specific aim, we will measure the impact of menopause on
ocular compliance and scleral mechanical properties in pre- and post-menopausal young (3-4 month) and
aged (9-10 month) female rats. This will allow us to assess how estrogen deficiencies alter the biomechanical
properties of the eye, which may impact RGC survival. In our second specific aim, we will evaluate the effect
of early and late menopause in rats with experimental glaucoma/ocular hypertension. Specifically, over 12
weeks, we will investigate functional visual impairment (e.g. visual acuity and contrast sensitivity), RGC
function and anatomical changes in the eye due to experimental glaucoma. Further, we will investigate the
potential therapeutic benefits of estrogen in female and male rats with experimental glaucoma. This will allow
us to determine whether estrogen therapy can preserve visual function after inducing experimental glaucoma.
Our third specific aim will examine the impact of menopause on inflammatory markers and protease
expression in the eye. We will also assess if the inhibition of inflammatory and protease expression prevents
changes in ocular compliance associated with menopause. This investigates the potential mechanism(s) that
an estrogen deficiency induces changes in ocular biomechanical properties. Our preliminary data support this
overall hypothesis. We expect to build off these strong data and find that menopause will differentially
influence the biomechanical properties of the eye, with young animals having a larger impact from an estrogen
deficiency. We also anticipate finding that post-menopausal rats have more severe visual impairment
compared to pre-menopausal rats and that estrogen therapy will preserve visual function in post-menopausal
females and aged m...

## Key facts

- **NIH application ID:** 10833997
- **Project number:** 5IK2RX002342-06
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Andrew J Feola
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833997

## Citation

> US National Institutes of Health, RePORTER application 10833997, The Effect of Estrogen Deficiencies on Vision Loss in Glaucoma (5IK2RX002342-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10833997. Licensed CC0.

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