Dr Joe Rainger received a Fight for Sight fellowship to find how genetic mutations cause ocular coloboma. His work will give more families answers to what caused their child’s coloboma, and could one day help prevent the sight loss the condition brings.
What is ocular coloboma?
Ocular coloboma is one of the most common eye malformations. One common indication is that a part of the iris is missing, leaving a misshapen pupil. However, problems may extend into the retina and optic nerve. As a result, coloboma is a major cause of life-long sight loss.
Like other conditions present at birth, gene mutations are an important contributor towards coloboma. But scientists are yet to identify most of the genes affected. This means parents often can’t be told what caused their child’s coloboma, leaving them with worry and unanswered questions.
“I don't think it can be overemphasised how important it is for a family to know that their child’s condition is anybody’s fault.
“I have always felt that, as a parent myself, it is very important to be able to provide that information, to be able to say, ‘You're very unlucky. You have this because of a genetic defect that nobody could have seen or known about’.”
The gap in our knowledge
Dr Joe Rainger works at the Roslin Institute in the University of Edinburgh. He received an Early Career Investigator Award from Fight for Sight to identify genes involved in ocular coloboma. To do this, Joe needed to learn more about eye development in the embryo.
Until the seventh week of pregnancy, the eye is open at the bottom. To form the eyeball correctly, the two sides of the gap must fuse like a zip. This is called optic fissure closure, and when this goes wrong, it causes coloboma.
But before Joe’s work, little was known about which genes controlled optic fissure closure. This meant it was difficult to say with certainty whether any mutations found in children were really responsible for their coloboma, or were just ‘innocent bystanders’.
Revealing eye development
To close this knowledge gap, Joe used chicken embryos to study eye development. Chicken embryos have relatively large eyes from early on, making it easier to see the eye forming, and to dissect tissue.
Joe discovered several genes that were activated during optic fissure closure. One called Netrin 1 was switched on when the edges of the gap were fusing, and switched off immediately after.
A colleague in London found Netrin-1 was also present in human embryos, in the right place at the right time during eye development. American collaborators also showed that switching off Netrin-1 in mice or fish caused colobomas.
Together, these discoveries indicated for the first time that Netrin-1 is a key gene in optic fissure closure and coloboma.
Information and prevention
Joe continues to study Netrin-1 and other genes, which he hopes will help more families understand what caused their child’s coloboma. This will not only give reassurance, but also enable other family members to be tested.
Joe is also investigating whether illness or vitamin deficiencies during pregnancy contribute towards coloboma. Understanding the causes of the condition – genetic and non-genetic – could eventually lead to interventions to prevent colobomas and the visual impairment they bring.
“If you have this condition, I think it must be reassuring to know that there are people like me who are passionate about understanding coloboma. It’s not just an academic exercise. It’s to try and help understand what the causes of these human birth defects are.”
How fellowships benefit research
As well as his scientific achievements, Joe’s fellowship helped him obtain further competitive funding to build his own research team. Through his collaborations, Joe has created a global community of coloboma researchers. All of this he puts down to the early support he got from Fight for Sight.
Joe’s story is one example of how backing promising early-career researchers with fellowships benefits the whole eye research community.
“(Early-career researchers) bring a brand-new perspective to an age-old problem, and I think that’s really powerful.”
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