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Advisory Committee Chair

Jason J Nichols

Advisory Committee Members

Pablo Argueso

Stephen Barnes

Susan Bellis

Kelly K Nichols

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) School of Optometry

Abstract

Mucins on the ocular surface are found in the tear film and are attached to corneal and conjunctival epithelial cells on the eye. The bulbar conjunctiva of the ocular surface can be divided into four anatomical regions: temporal, superior, nasal, and inferior. The palpebral conjunctiva is the epithelial layer of the inner surfaces of the upper and lower eyelids. In the tears, mucins provide lubrication of the ocular surface through formation of a hydrophilic gel. The primary mucin in the tear film is MUC5AC which is secreted by goblet cells that are located in varying densities within the bulbar conjunctiva. On the apical surface of the eye, membrane associated mucins (MAMs) form a protective barrier known as the glycocalyx. The highly O-glycosylated MAMs in the glycocalyx create a hydrophilic surface that attracts the tear film. The MAMs identified on the human ocular surface in the superficial cell layers, represented by “MUC” followed by a number representing order of discovery, are MUC1, MUC4, and MUC16. These mucins are expressed and secreted by the corneal and conjunctival epithelial cells. Galectin-3, a β-galactoside binding lectin, recognizes the carbohydrate galactose found on MUC1 and MUC16 and colocalizes with these MAMs in the glycocalyx. Galectin-3 is an essential component of the glycocalyx as without it, barrier function is impeded. In dry eye disease, inflammation is a core mechanism that can have negative consequences on the ocular surface. Chronic inflammation can lead to damage to the epithelial cells and tear film instability resulting in poor ocular surface hydration. Reduction of goblet cells and reduced MUC5AC are potential contributing factors to dry eye disease. The glycocalyx and glycosylation of the MAMs may also be negatively impacted such that the glycocalyx becomes disrupted. The primary purpose of this research was to investigate expression of MAMs in the regions of the bulbar conjunctiva and the palpebral conjunctiva of the upper eyelid. In addition, the secondary goal of this research was to develop an affinity assay for in vivo use on human tear samples that would enable researchers to evaluate the affinity of the interaction of MUC16 and galectin-3.

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