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Advisory Committee Chair

Kelly K Nichols

Advisory Committee Members

Jianzhong Chen

Jason J Nichols

Steven Pittler

Mark Willcox

Document Type

Dissertation

Date of Award

2020

Degree Name by School

Doctor of Philosophy (PhD) School of Optometry

Abstract

Once thought to be no more than a vexing eye condition, ocular surface disease (OSD) is now being viewed as a differentiating factor between sight and no sight. In the setting of glaucoma, OSD can interfere with treatment success, potentially allowing the visually devastating pathology of glaucoma to plow onward with little restraint. Compounding the clinical challenge is the growing awareness that glaucoma-associated OSD appears to be iatrogenically induced by topical ophthalmic medications. Daily, topical instillation of preserved prostaglandin analogs (PGAs), the most common first-line treatment for glaucoma, has been linked to a variety of OSD subtypes, including meibomian gland dysfunction (MGD). The mechanisms that underlie these associations are poorly understood. The purpose of this dissertation project was to test the hypothesis that prostaglandins (PGE2 and PGF2α), a representative PGA (latanoprost), and its preservative system (benzalkonium chloride [BAK]) impose cytotoxic effects on and modulate lipid expression from immortalized human meibomian gland epithelial cells (HMGECs). To accomplish these goals, experimental methodology needed to be refined to optimize nonpolar lipid extraction from cell lysates, to adapt harvesting protocols to improve efficiency, and to test the differentiating capacity (as measured by lipidomic expression) of purported differentiating agents. Chapter One provides a comprehensive overview of background information pertinent to glaucoma-associated MGD and presents pilot work that supports the design of this project. Chapters Two through Four describe the development of experimental methodology specific to lipid analysis from HMGECs. Chapters Five and Six, building upon this formative work, apply these methods to the crux of this research project: elucidating the mechanisms of iatrogenic MGD in glaucoma. Chapter Five evaluates the physiologic effects of PGE2 and PGF2α on HMGEC viability and lipid expression. Chapter Six explores the pathophysiologic effects of latanoprost, BAK, and the combination of the two on the same parameters. The final chapter, Chapter Seven, summarizes and integrates the results of this work, placing it within the context of current literature. Chapter Seven, as well as this dissertation as a whole, closes with forward-looking statements, new hypotheses, new research directions, and applications to clinical practice.

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Optometry Commons

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