Nina Sara Fraticelli-Guzmán, MS

BioE PhD Proposal Presentation

1-2pm on Tuesday, June 10, 2025

Location: EBB CHOA Room #1005

https://gatech.zoom.us/j/92302500443

(Meeting ID: 923 0250 0443)

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Committee:

Andrew J. Feola, PhD (Advisor) (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University; Department of Ophthalmology, Emory University; Atlanta VA Medical Center for Visual & Neurocognitive Rehabilitation)

C. Ross Ethier, PhD (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University)

Todd Sulchek, PhD (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology)

Levi Wood, PhD (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology)

W. Daniel Stamer, PhD (Department of Ophthalmology, Duke University)

Menopause-induced changes to the biomechanics and gene expression profile of the outflow pathway

Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by peripheral vision loss due to retinal ganglion cell (RGC) loss. It’s projected to affect 112 million people by 2040, and 59% of the glaucomatous population are women. Past work suggests menopause, a hormonal process unique to females, that results in the decline of circulating estrogen and progesterone, might be a sex-specific factor associated with glaucoma.

Recent work found that the age onset of menopause had a linear association with the timing of glaucoma diagnosis. Other works have found that early-onset menopause increases the risk of developing glaucoma later in life and that menopause impacts intraocular pressure (IOP) – the only modifiable risk factor for glaucoma. Further, estrogen has been identified as an upstream regulator for genes associated with IOP, called IOP-associated genes. However, menopause’s role, particularly early-onset menopause, in glaucoma development is still not well understood. This work will address this gap by characterizing the potential impact early-onset menopause has over time on IOP, eye biomechanics, and gene expression associated with IOP and glaucoma.

Working with Brown Norway rats, Aim 1 will focus on determining the impact of early-onset menopause over time on IOP and aqueous humor (AH) outflow resistance. Aim 2 will investigate early-onset menopause’s impact on the stiffness of the trabecular meshwork’s (TM) distinct segmental flow regions (high flow (HF) and low flow (LF)), the major tissue helping regulate aqueous humor flow within the eye. Aim 3 will assess gene expression changes within the TM induced by early-onset menopause. We hypothesize that over time, early-onset menopause increases IOP via increased AH outflow resistance and TM stiffness that are mediated by IOP-associated gene expression. This will provide insight into how early-onset menopause is related to factors associated with glaucoma over time and potentially identify menopause-associated pathways for new treatment targets for all glaucomatous patients.