A fresh focus on personalised treatments for eye disease
Losing your vision over time has a profound impact on day-to-day life. Many conditions can cause such loss of vision, from rare inherited disorders to diabetes damaging blood vessels in the eye, glaucoma and age-related degeneration. In the coming years, we will hopefully see new treatments for many causes of vision loss, but to get there, we need to understand why the eye breaks down and stops working.
That’s why the EYE-D project is digging deep into the molecular causes of eye disease, with the aim of finding new ways to slow or even stop eye disease.
Led by Trinity College scientists Professor Sarah Doyle and Professor Matthew Campbell and Eye & Ear clinician Dr Mark Cahill, and funded by SFI and industry partners to the tune of €3.2 million over four years, EYE-D is looking to patients for clues about why the eye loses vision over time, and using those findings to explore questions more deeply in the lab.
“In the rare retinal diseases we sometimes know the genetic cause of the sight loss, but for conditions like glaucoma and diabetic retinopathy and age-related macular degeneration or AMD, which are really common forms of blindness, we generally don’t know the exact molecular cause, we don’t know the key drivers of what is causing the disease,” explains Professor Campbell who is Professor of Genetics at Trinity College Dublin.
“So a central focus of this project is to tease apart the actual molecular components, the causative agents of these diseases. We hope this will help us to identify new targets that the pharmaceutical industry can then use to design the drugs of the future that will treat these diseases and save people’s vision.”
While many molecular studies of disease start looking in cells in the lab and eventually progress to patients, EYE-D is taking a more agnostic approach and carrying out lab and patient studies alike.
“We are doing clinical research with patients already,” says Professor Campbell, who notes the importance here of two project partners in particular - charity Fighting Blindness Ireland and clinical research facility Progressive Vision Research.
“We are recruiting patients who are at a really early or intermediate stage of disease and we can take detailed images of the retina at the back of their eye, following up with them over years to see what is happening at a molecular level.”
The researchers are using these findings to inform their experiments in cells in the lab, teasing out the molecular drivers and pathways that are leading to sight loss, he adds. “In these lab models we can measure what genes are being switched on and off, looking for clusters of pathways that are driving the development of the disease.”
Other studies of the brain are also helping to point the way, notes Professor Doyle, who is based at the Trinity College Dublin Institute for Neuroscience.
“The retina at the back of the eye is an extension of the brain,” she explains. “We know a number of key pathways that have been discovered to be really important for degeneration in brain diseases, so we are now looking at whether these same pathways could also be important for degeneration in the retina. If through our various studies we can discover the important molecular drivers, then we can bring those to our industry partners at Roche and Eli Lilly, and they can use them to develop potential treatments against blindness.”
The goal is to translate at least one of the targets into early clinical testing by the end of the project, says Professor Campbell, and that the understanding we get from the research will help to inform more personalised approaches to treatment in the future. “In the next 15-20 years we expect to see a multi-drug approach to treat the different stages of eye diseases,” he says.
“And ideally we will have precision medicine-based approaches where we can understand in intimate detail an individual’s rate of retinal degeneration and then match them with the most appropriate treatment against the molecular drivers of their disease. In order to do that, we need to know what those drivers are.”