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Abstract
A corneal erosion is created by a full thickness loss of corneal epithelium. They are painful, increase the risk of infection, and can lead to discontinuation of contact lens wear. Understanding their aetiology would assist in managing this important adverse event.
In non-contact lens wearers, a collagen degrading enzyme known as matrix metalloproteinase-9 (MMP-9) has been found to be upregulated in the corneas of those prone to erosions. MMP-9 is thought to weaken corneal adhesion complexes, contributing to the cascade of events leading to erosions. This thesis investigates the effect of contact lens wear on MMP-9 and its regulators in the tear film.
In this study, a flush tear collection technique was first validated against basal and reflex tear collection. This permitted rapid and repeatable retrieval of the major proteins in the same proportions as occurs in basal tears.
Tears were collected from healthy, non-contact lens wearers to establish the diurnal variation of MMP-9 and its regulators. Eye-closure resulted in a 200-fold increased expression of MMP-9 compared to only a 3- and 5-fold increase in its regulators TIMP 1 and NGAL, respectively. After the first night of extended contact lens wear, MMP-9 increased significantly compared to baseline and daily wear, with no change in its regulators. This increase in MMP-9 returned to baseline after one month.
Differential gel electrophoresis was used to gauge the effect of extended wear on the tear proteome. Changes were identified in serum albumin, immunoglobulin A and zinc α2-glycoprotein, while other major proteins were largely unaffected.
The tears of three contact lens wearers who developed erosions were compared to normals. A greater MMP-9:TIMP-1 ratio was found upon awakening, both at baseline and after the first night of contact lens wear compared to normals. Elevated NGAL at baseline that further increased after the first night of extended wear was also found in one participant. The tear proteome profile also changed significantly after the first night of extended wear in one participant.
These studies demonstrated increased expression of MMP-9 in response to extended contact lens wear. This increase may predispose the cornea to adverse events during the early stages of extended wear.