Overview
Trachoma is a condition that first affects the upper eyelid and can lead to complications from scar tissue. It’s the leading infectious cause of blindness worldwide and is a major health problem in over 50 countries. 40 million people have active trachoma (meaning they have a current infection), with 8.2 million in need of surgical treatment.
The condition is triggered by repeated infection of the lining of the eyelids (the conjunctiva) in childhood with bacteria called Chlamydia trachomatis. This causes long-term inflammation. The infection can be cured with antibiotics, but trachoma still often progresses. The eyes get inflamed and scar, the upper eyelid turns inwards and the eyelashes rub on the front surface of the eye (the cornea). This is painful and eventually leads to blindness. Although it can be partly treated by surgery, the condition usually comes back after a few years. There is no treatment available, and very little is known about how and why it progresses.
Dr Bailly’s team has a lot of expertise in studying scarring and contraction in conjunctiva and in this project they are aiming to find out more about how it happens. They are comparing the genes that are active in healthy cells with those in cells with trachoma and are hoping to identify the main molecules that drive trachoma to continue, as these could be new targets for developing treatment.
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Publications
- Kechagia JZ, Ezra DG, Burton MJ, Bailly M. Fibroblasts profiling in scarring trachoma identifies IL-6 as a functional component of a fibroblast-macrophage pro-fibrotic and pro-inflammatory feedback loop. 2016 Jun 20
- Li H, Ezra DG, Burton MJ, Bailly M. Doxycycline prevents matrix remodeling and contraction by trichiasis-derived conjunctival fibroblasts. Invest Ophthalmol Vis Sci. 2013 Jul;54(7):4675–82.
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Research update
In this project the team developed a useful way to study the differences between healthy cells and ones from people with scarring trachoma, by growing the cells in gel containing the protein collagen. This is the protein we have most of in the body – it forms connective tissue that holds the body together and is also a big part of scar tissue.
The team found that the trachoma cells were more able than healthy cells to make scar-like tissue, by producing more collagen. The team also found another protein that seems to be involved in scarring and is also linked to cancer. We don’t know exactly what it does yet, but the team is trying to find out. Importantly, they have also identified the antibiotic doxycycline as a treatment that could help trachoma from returning after surgery.
Most recently, the team has found evidence that the immune system is active in conjunctival connective tissue from people with scarring trachoma even when there's no infection. Inflammation and scarring seem to form a positive feeback loop that could be the reason why the condition can worsten for years. -
Scientific summary
Signal transduction pathways in trachoma related fibrosis: characterisation and therapeutic implications
Trachoma is a scarring disease of the upper eyelid, which is the leading infectious cause of blindness worldwide. The condition is triggered by repeated childhood conjunctival infections with the bacterium Chlamydia trachomatis, which causes chronic inflammation. Whilst the infection itself can be eradicated with biannual single doses of azithromycin, the disease often progresses, even in areas where little or no C. trachomatis infection can be detected. The progressive fibrosis leads to turning of the eyelid inwards and causes the eyelashes to rub on the cornea (trichiasis), eventually causing corneal opacification and blindness.
Following trichiasis surgery, the anatomical abnormality frequently re-develops, in part through an ongoing immuno-fibrogenic process. There are currently no adjuvant treatments available to suppress the pro-fibrotic state and reduce recurrence and very little is known about the molecular mechanisms underlying disease progression and recurrence.
This project uses trachomatous biopsies taken at the time of trichiasis surgery to establish a model of conjunctival fibrosis and contraction. The team are using the model to characterise the functional phenotype of trachomatous conjunctival fibroblasts in terms of contractile force and matrix remodelling and to identify pro-fibrotic signalling pathways in trachomatous fibroblasts using a genome-wide expression microarray platform. Results of the array will be validated using a variety of assays that the team has developed. This study aims to provide much needed information on the molecular mechanisms underlying the pathogenesis of scarring trachoma and will allow us to identify and test new targets for therapeutic intervention against the disease process.