Thanks to funding from Fight for Sight, a team from the University of Aberdeen has laid the groundwork for a potential new cell therapy for uveitis.
This therapy could represent a long-lasting cure without the side effects of current treatments.
Uveitis is inflammation in the eye and causes 15% of all blindness.
While half of cases are caused by infections, the other half result from a hyperactive immune system attacking the retina. Uveitis is treated with immunosuppressant drugs, but these drugs can cause significant side effects and don’t always work.
Controlling the immune system
As an alternative, scientists funded by Fight for Sight are exploring cell therapies, including cells called T-regulatory cells or ‘T-regs’.
T-regs are the counterpart of T-cells, the ‘killers’ of the immune system, which seek and destroy infected cells in the body. T-regs provide balance, limiting the T-cell attack before it gets out of hand.
It’s thought that T-regs could hold the key to restoring control to the immune system and so stop uveitis.
“The ultimate aim is a new therapy for uveitis, without the side-effects.”
The role of Fight for Sight
At the University of Aberdeen, Prof Heather Wilson and her team study how immune-mediated diseases like uveitis develop, including the role that T-regs play.
One of Prof Wilson’s colleagues, Prof John Forrester, had worked with Oxford scientists on a genetically-engineered mouse that develops uveitis. They had discovered the mouse had low numbers of T-regs.
Prof Forrester suspected that, without enough T-regs, the T-cells go out of control and trigger the uveitis.
Profs Wilson and Forrester teamed up with uveitis expert Dr Lucia Kuffová to test this idea. Together, they were awarded a grant in 2018, jointly funded by Fight for Sight and the Scottish Chief Scientist Office (CSO).
Preventing uveitis with T-regs
During the project, the Aberdeen team found they could prevent uveitis from developing in the mice by transferring T-regs from another mouse with active uveitis.
Dr Christine Moelzer from Prof Wilson’s team also made discoveries that mean, in a future treatment for humans, you could use a patient’s own T-regs. In theory, their T-regs could be removed, activated, and multiplied in a lab and then re-infused back into their body, reducing the risk of side effects.
Download our research strategy and discover more about how we are funding brilliant minds to better understand, diagnose, prevent and treat eye disease.
A surprise link to the bowel
One surprising discovery was the mice develop inflammatory bowel disease as well as uveitis. Though it was already known the two conditions often go hand-in-hand, the team found a potential explanation why.
In the mouse, they think a molecule which triggers the uveitis in the eye might travel to the bowel, and cause inflammation there. This in turn amplifies both diseases, in a vicious circle. The team plan to investigate whether this happens in humans.
The potential for a cure
Prof Wilson’s team have a lot more work to do before a T-reg cell therapy is ready for human clinical trials. But they have shown it has huge potential for treating uveitis.
Current treatments can only control the disease for a while, if at all. In contrast, T-reg cell therapy could be a long-lasting cure, with few side-effects.
“The immune system in these patients is out of control,” says Prof Forrester. “What we’re trying to do is reset the immune system, through natural means.”
Prof Wilson says the funding from Fight for Sight and the Scottish CSO was “hugely important” for this work. “We wouldn’t have been able to get to this stage without it.”
“It’s funding like this that is making the breakthroughs. This can start in university labs and then lead to bigger things, but we need those initial ideas tested out. It is absolutely essential.”
Stay in the loop
on eye research breakthroughs, inspiring real life stories and more...
Related content
