Scientists discover genetic changes linked to a major risk factor for blinding trachoma
Aiming to understand why the effects of brief infections are so long-lasting in the world’s leading infectious cause of blindness
Researchers funded by Fight for Sight have found another clue to how the world’s leading infectious cause of blindness does its damage. The team at the London School of Hygiene & Tropical Medicine, together with colleagues in West Africa, has identified changes in the early stages of infection to specific molecules that control gene activity. The changes could make it more likely that children will go on to develop the condition in its long-term, severe form.
Trachoma is widespread in 51 countries and is the cause of irreversible blindness in 1.2 million people worldwide. Mass distribution of antibiotics can successfully treat the initial stage when bacteria called Chlamydia trachomatis infect the membrane that covers the front of the eye and lines the inside of the eyelids (the conjunctiva).
Long-term inflammation and scarring
But children in areas where trachoma is rife can become infected repeatedly. In some, this triggers long-term inflammation and scarring of the eyelid.
Scars make the eyelids tighten which can make eyelashes turn inward and scratch the cornea – a condition called trichiasis. Eventually the usually clear front surface of the eye (the cornea) becomes clouded and blinding.
So the research team wanted to find out what makes the process of inflammation and scarring continue in some people but not others. Their earlier research found changes 2 specific molecules that control gene activity (microRNAs). The microRNAs known as miR-147b and miR-1285 are increased in adults with scarring and inflammatory trachoma. And their new study is the first report of microRNA activity in inflammatory trachoma during the first stage of the condition.
Results showed that 2 microRNAs – miR-155 and miR-184 – have a direct relationship with the degree of inflammation, in samples from children with both infection and inflammation compared to samples from children with healthy conjunctiva and no infection.
Immune system activity
“What we found is that miR-155 is increased and miR-184 is decreased as the severity of clinical inflammation goes up,” says first author and Fight for Sight PhD student, Tamsyn Derrick from the London School of Hygiene & Tropical Medicine. “We think this pattern of microRNA expression reflects the activity of immune cells in the conjunctiva. MiR-155 in particular has wide-ranging and profound effects on immune cell development and function, while miR-184 is the only microRNA that is present in significantly different levels between people with inflammatory trachoma that has persisted post-infection, versus uninfected healthy controls.”
“Inflammation is known to be a major risk factor for scarring trachoma and these results give us an important indication of why,” said Dr Dolores M Conroy, Director of Research at Fight for Sight. “One of the priorities for research identified by .the Sight Loss and Vision Priority Setting Partnership was to find out whether severe ocular surface diseases in children can be better managed. Knowing who is at risk and how that risk can be reduced is a major step towards better management of this globally devastating condition.”
The research is published in open-access journal BMC Infectious Diseases and also received funding from the Wellcome Trust.
Read the full press release (PDF).
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