Cydney Wong
BME PhD Defense Presentation

Date: 2025-11-14
Time: 11:00 AM - 1:00 PM
Location / Meeting Link: IBB 1128 / https://gatech.zoom.us/j/92608495211?pwd=jG5caaWBeat8c7DO0nGvh5yluN9rKh.1

Committee Members:
C. Ross Ethier, PhD (Advisor); Andrew Feola, PhD; Levi Wood, PhD; Todd Sulchek, PhD; Edward Botchwey, PhD; W. Daniel Stamer, PhD 


Title: Biomechanical and Transcriptional Analysis of Segmental Outflow and Ocular Hypertension

Abstract:
Glaucoma is the leading cause of irreversible blindness, and the most common form of glaucoma is primary open-angle glaucoma (POAG). The main risk factor for developing most forms of glaucoma is elevated intraocular pressure (IOP), which is maintained by the rate of production and the resistance to outflow of aqueous humor from the anterior chamber of the eye. The trabecular meshwork (TM) is a main regulator of aqueous humor outflow and IOP homeostasis. AH outflow around the circumference of the eye is non-uniform, i.e. there are high flow (HF) and low flow (LF) regions within the TM. This phenomenon, known as segmental flow, occurs in both normal and glaucomatous eyes, but the mechanisms underlying segmental flow are unknown. Better understanding of the functional and molecular differences between HF and LF regions could shed light on aqueous humor outflow regulation and inform development of more targeted IOP-lowering therapies. This thesis investigates biomechanical and transcriptomic differences between HF and LF regions of the TM using mouse and human tissue. In Aim 1, we quantified segmental flow patterns in normal and dexamethasone-induced (DEX) ocular hypertensive mice and found differences in flow distribution but no change in the overall proportion of high versus low flow regions. In Aim 2, we assessed HF versus LF TM stiffness and matrix composition in normal and DEX-treated mice and found no stiffness differences between regions, although DEX treatment increased TM fibronectin and alpha-SMA levels relative to controls. In Aim 3, we performed transcriptomic profiling of HF and LF regions in non-glaucomatous human and mouse TM and identified differential expression of several glaucoma-associated genes, as well as differential enrichment of cellular stress- and epigenetics-related pathways. Together, these findings provide new insights into segmental outflow in both mouse models of glaucoma and human eyes and identify candidate mechanisms that could support the development of more precise IOP-lowering strategies for POAG