Advisory Committee Chair
Jason J Nichols
Advisory Committee Members
Champion Deivanayagam
Steven J Pittler
Mark D P Willcox
Hui Wu
Document Type
Dissertation
Date of Award
2021
Degree Name by School
Doctor of Philosophy (PhD) School of Optometry
Abstract
Glycoprotein 340 (Gp340) is a 340-kDa multi-domain pattern recognition receptor (PRR) belonging to the scavenger receptor cysteine-rich superfamily of proteins. On the ocular surface, Gp340 is expressed in the tear film, lacrimal gland, cornea, and conjunctiva. By their nature, PRRs detect pathogen-associated molecular patterns (PAMPs) on microbial organisms and damage-associated molecular patterns (DAMPs) released from injured, stressed, necrotic, and apoptotic cells. This, in turn, induces the expression of nuclear factor-κB- and the interferon regulatory factor-dependent expression proinflammatory cytokines and chemokines, eliciting both innate and adaptive immune response activation. Thus, as a PRR, Gp340 has the potential to modulate microbial infection and inflammatory processes on the ocular surface. Consistent with this hypothesis, Gp340 expression in tear fluid has been shown to be dysregulated in dry eye, an ocular surface disease that is characterized by tear hyperosmolarity and chronic inflammation. In addition, Gp340 inhibits twitching motility of P. aeruginosa and promotes corneal epithelial wound healing. These findings suggest that Gp340 plays an important role in the pathophysiology of dry eye disease and could modulate events related to ocular surface infection. iv The goals of this dissertation research were to (1) investigate the expression of Gp340 in human corneal epithelial cells (HCECs) under hyperosmolar stress, and its role in the pathophysiology of dry eye inflammation, (2) determine the effect of Gp340 on the adhesion of infectious P. aeruginosa and S. aureus strains to contact lens polymers, and (3) examine the expression pattern of Gp340 in HCECs infected with P. aeruginosa and S. aureus, two major microbial keratitis etiological agents. Chapter 1 presents an overview of dry eye disease, Gp340, and Gp340’s known roles in dry eye, infection, and contact lens-related adverse events. It highlights the justification and need for this research, specific aims, and hypotheses. Chapter 2 is an extensive review of the expression and roles of Gp340 in wet-surfaced mucosal immunity and on the ocular surface. Chapters 3 – 5 described studies on the three specific aims which tested the hypotheses of the proposed research. Summary and conclusions are provided in Chapter 6 with an outlook for future research.
Recommended Citation
Osei, Kwaku Antwi, "Glycoprotein 340 Expression in Dry Eye Disease and Ocular Surface Infection" (2021). All ETDs from UAB. 557.
https://digitalcommons.library.uab.edu/etd-collection/557
