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Surface-Active Synthetic Glycocalyx and Lipid Layer Analogs for the Treatment of Dry Eye Disease

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Abstract

Dry Eye Disease (DED) is one of the most prevalent ophthalmic diseases and caused by an unstable tear film. The tear film is made of three sequential layers: mucin (or glycocalyx), water, and lipid layers listed from innermost to outermost, respectively. When a deficiency in one of these layers is present, it leads to DED. There are several treatment options that currently exist for DED but they do not provide long-lasting relief as they only target one layer of the tear film. Surface tension and viscosity are two mechanical measurements that influence tear film stability as shown by mathematical models. The tear film can be stabilized by reducing the surface tension (targeting the lipid layer) or by increasing the viscosity. The viscosity can be increased by having sugars in solution that crosslink with Galectin-3, a carbohydrate binding protein found naturally in the tear film and is increased in DED patients. A polymer library was synthesized to target multiple layers of the tear film by having a polymer backbone (polyacrylic acid) as well as sugar (lactose) and lipids (C12 and C16) conjugated to the backbone. To increase tear film stability, lactose was used to crosslink with Galectin-3 to increase the viscosity and the lipids were used to decrease the surface tension. The lipids could also bind to the corneal epithelium to stabilize the glycocalyx. This project had three aims. Aim 1 was to synthesize a library of lipo-glycopolymers with changes in lipid type, as well as sugar and lipid density. Aim 2 was to measure the viscosity and surface tension of the polymers to understand how they compare to DED products available. Aim 3 was to analyze the polymer’s efficacy to stabilize a thin film both experimentally as well as theoretically. A novel experiment was created to measure the breakup time and it was also calculated using the viscosity and surface tension values from Aim 2. The polymers had a lower surface tension than commercial solutions and viscosities similar to natural tears. As the calculated breakup time for the polymers increased, so did the experimental breakup time, which was expected.

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Description

149 pages

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Date Issued

2023-08

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Keywords

Dry Eye Disease; polymer; Tear film

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Union Local

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Committee Chair

Putnam, David

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Committee Member

Alabi, Christopher
Ledbetter, Eric

Degree Discipline

Biomedical Engineering

Degree Name

Ph. D., Biomedical Engineering

Degree Level

Doctor of Philosophy

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Government Document

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Attribution 4.0 International

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dissertation or thesis

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