Date on Master's Thesis/Doctoral Dissertation

5-2022

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemistry

Degree Program

Chemistry, PhD

Committee Chair

Borchman, Douglas

Committee Co-Chair (if applicable)

Maurer, Muriel

Committee Member

Zamborini, Frank

Committee Member

Zhang, Xiang

Author's Keywords

Spectroscopy; cholesteryl ester; wax ester; dry eye; tear film; lipid

Abstract

The major aim of my dissertation was to investigate the etiology of dry eye disease which affects about 7 million people in the United States, causing symptoms that can lead to visual disturbance. Correlation between dry eye and an abnormal lipid layer of the tear film has been found. Tear film lipids originate mostly from the meibomian glands. Cholesteryl ester (CE) and Wax ester (WE) lipids make up most of the human meibum lipidome and the CE/WE ratio has been shown to decrease in patients with meibomian gland dysfunction. Model studies using synthetic CE and WE, although providing some insight, are weak in their application as human CE and WE contain variable amounts of hydrocarbon chain branching, saturation and chain lengths. It is thus almost impossible to model the diverse composition of human meibum lipids using synthetic WE and CE. In vitro model studies of meibum lipids were therefore conducted using adsorption column chromatography, 1H-NMR, and FTIR spectroscopies to investigate meibum lipid interactions and the relationships between meibum lipid conformation and composition changes. Interactions between synthetic minor meibum lipids and hyaluronic acid (HA) were also investigated to identify practicable relevance to dry eye treatment. HA is used in eye drops with other therapeutics for dry eye symptoms mitigation. Data suggest physiological levels of HA, PC and SM may be related eye drop therapy. Human meibum CE and WE were also completely separated and spectroscopically verified. Phase transitional data of CE/WE mixtures indicated that CE changes the phase characteristics of meibum depending on whether it is more or less ordered than WE. Changes in the meibum CE/WE ratio could therefore explain changes in meibum order with age and meibomian gland dysfunction (MGD) which may influence tear film stability. CE/WE ratios from the meibum of donors with Sjögren syndrome were also compared to meibum from donors without dry eye to better understand the relationships between dry eye disease and meibum compositional differences.

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