Abstract
BackgroundSurgery for trachomatous trichiasis (TT) is a key component of the SAFE Strategy for trachoma control. Unfortunately, recurrent TT following surgery is common, probably due to various surgical and disease factors. To develop strategies to reduce recurrence rates it is necessary to understand its pathological basis. In this study we investigated the relationship between recurrent trichiasis and the expression of various cytokines and fibrogenic genes during a two-year follow-up period.Methodology/Principal FindingsIndividuals undergoing surgery for TT were examined at baseline (pre-operative), 6, 12, 18 and 24 months. Conjunctival swab samples were collected from the tarsal conjunctiva for RNA isolation on each occasion. Individuals who developed recurrent TT with at least 3 lashes touching the eye on one or more occasion were designated “cases” and an equal number of “controls” were randomly selected from those without recurrent TT, frequency matched for age and baseline TT severity. The expression of the following genes was measured by quantitative RT-PCR: S100A7, IL1B, CXCL5, TNFA, NOS2A, CTGF, MMP7, MMP9 and MMP12. Thirteen hundred individuals were enrolled and underwent surgery. By two years 122 had developed recurrent TT with at least 3 lashes touching the eye. Recurrent TT was consistently associated across multiple time points with about a 2-fold increase in S100A7 expression (p = 0.008). Clinically visible conjunctival inflammation was associated with increased S100A7, IL1B, CXCL5, MMP9 and MMP12 expression.Conclusions/SignificanceIncreased S100A7 expression was associated with trachomatous conjunctival scarring and may be linked to the pathophysiology of recurrent TT. S100A7 expression could be a potential biomarker for this disease process. As part of the epithelial innate immune response S100A7 has multiple actions, potentially contributing to a chronic pro-inflammatory response, which may lead to ongoing tissue damage and increased scarring.
Highlights
Trachoma remains the leading infectious cause of blindness worldwide [1]
As there was no difference in the trachomatous trichiasis (TT) recurrence rate between the two alternative sutures, subjects for this nested case-control study were drawn from both trial arms and data combined [12]
Comparing the eligible and excluded people: there was no difference in the proportion who were female (p = 0.3), the eligible group was slightly younger (49 years vs. 51 years, t-test p = 0.02) and had slightly more severe baseline trichiasis
Summary
Trachomatous Trichiasis (TT) is the potentially blinding stage of this disease in which the eyelashes scratch the surface of the globe, resulting in corneal opacification [2,3,4]. It is the result of a progressive scarring process of the tarsal conjunctiva, which is initiated in childhood by recurrent episodes of Chlamydia trachomatis infection that are characterised by inflammation. Recurrence, which may be defined as that developing within the first six months following surgery, appears to occur with a greater incidence rate than late recurrence [9]. Recurrent TT following surgery is common, probably due to various surgical and disease factors. In this study we investigated the relationship between recurrent trichiasis and the expression of various cytokines and fibrogenic genes during a two-year follow-up period
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