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Title: Pro-fibrotic and pro-inflammatory properties of scarring trachoma fibroblasts
Author: Kechagia, Z.-Z.
ISNI:       0000 0004 8502 4449
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Trachoma is the leading infectious cause of blindness worldwide, and one of the oldest diseases ever recorded. The initiation of the disease is caused by Chlamydia trachomatis and after an initial phase of infection and chronic inflammation (active trachoma), scarring develops and the eyelashes turn inwards (trichiasis), driving the blinding consequences of the disease. Because trichiasis occurs even after eradication of the bacterial infection, we hypothesized that trachoma scarring is due to functional alterations of the conjunctival fibroblasts. Using isolated scarring trachoma fibroblasts (STFs) from patients undergoing trichiasis surgery and matching control fibroblasts (CFs), we established an in vitro model to study fibroblasts responses to environmental stimuli. We found that fibroblasts from trichiasis patients had an increased ability to trigger tissue contraction, altered cell force responses and increased extracellular matrix remodelling ability compared to matching controls. In particular, they contracted more than controls in response to macrophage and PDGF stimulation, and were less potent to elicit M2 alternative macrophage activation. These suggested that they displayed a pro-fibrotic and pro-inflammatory phenotype that could be maintained in vitro. Microarray analysis of STFs and CFs, showed a total of 127 genes to be upregulated and 45 downregulated (> 2 fold change, Pvalue < 0.05 moderated t-test). These genes fell in three main categories of pro-fibrotic, pro-inflammatory and differentiation associated genes. We further examined the role of two of the most upregulated genes in our dataset namely IL-6 and LIMCH1 and their role in fibroblast-macrophage communication and cell motility respectively. Overall, our findings suggest an active involvement of fibroblasts in the scarring trachoma progression and immune response regulation. Moreover, the in vitro model that we have developed has proven to be a good system allowing us to study the functional characteristics of STFs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available