Abstract
PurposeTo characterize the histological appearance and expression of pro-inflammatory mediators, growth factors, matrix metalloproteinases and biomarkers of epithelial-mesenchymal transition (EMT) in healthy control and trachomatous trichiasis (TT) conjunctival tissue.MethodsConjunctival biopsies were taken from 20 individuals with TT and from 16 individuals with healthy conjunctiva, which served as controls. Study participants were of varying ethnicity and were living in a trachoma-endemic region of northern Tanzania. Formalin-fixed paraffin-embedded tissue sections were stained using hematoxylin and eosin or by immunohistochemistry using antibodies against: IL-1β, IL-6, IL-17A, IL-22, CXCL5, S100A7, cleaved caspase 1 (CC1), PDGF, CTGF, TGFβ2, MMP7, MMP9, E-cadherin, vimentin, and αSMA.ResultsTissue from TT cases had a greater inflammatory cell infiltrate relative to controls and greater disruption of collagen structure. CTGF and S100A7 were more highly expressed in the epithelium and IL-1β was more highly expressed in the substantia propria of TT cases relative to controls. Latent TGFβ2 was slightly more abundant in the substantia propria of control tissue. No differences were detected between TT cases and controls in the degree of epithelial atrophy, the number of myofibroblasts or expression of EMT biomarkers.ConclusionsThese data indicate that the innate immune system is active in the immunopathology of trachoma, even in the absence of clinical inflammation. CTGF might provide a direct link between inflammation and fibrosis and could be a suitable target for therapeutic treatment to halt the progression of trachomatous scarring.
Highlights
Trachoma is a blinding disease initiated by infection of the conjunctival epithelium with the intracellular bacterium Chlamydia trachomatis (Ct)
CTGF and S100A7 were more highly expressed in the epithelium and IL-1β was more highly expressed in the substantia propria of trachomatous trichiasis (TT) cases relative to controls
No differences were detected between TT cases and controls in the degree of epithelial atrophy, the number of myofibroblasts or expression of epithelial-mesenchymal transition (EMT) biomarkers
Summary
Trachoma is a blinding disease initiated by infection of the conjunctival epithelium with the intracellular bacterium Chlamydia trachomatis (Ct). Individuals living in trachoma-endemic communities are repeatedly infected with Ct, which causes a follicular conjunctivitis. Recurrent inflammation, even in the absence of detectable Ct infection, is associated with progressive scarring [1]. Trachoma is endemic in 51 countries and impairs the eyesight of 2.2 million people worldwide, 1.2 million of whom are irreversibly blind [2]. Trachoma control programs have made good progress in reducing active disease, there is some evidence that established scarring disease continues to progress even when chlamydial infection appears well controlled [1]. In order to develop a vaccine or therapeutic treatments to prevent the progression to trichiasis, a better understanding of the immunopathology of scarring trachoma is required
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