A team at TCD has found a way to deliver therapeutic drugs more easily into the retina at the back of the eye
WHEN IT comes to guest lists, your brain and retina rank among your body’s most exclusive clubs. They need a strict door policy – otherwise bacteria and viruses in your bloodstream could invade the delicate tissues and potentially wreak havoc.
But the tough bouncers that block the undesirables from the brain and eye can also keep out helpful agents that you might actually want to get there, such as drugs to target disease.
Now a group at Trinity College Dublin has developed a neat way to sneak therapeutic molecules past the velvet rope, and it could pave the way to more patient-friendly delivery of treatments for degenerative eye disease.
The main obstacle to overcome is the inner blood-retina barrier, explains Dr Matthew Campbell, a post-doctoral researcher at TCD’s department of genetics.
“The cells that line the blood vessels contain tight junctions that prevent the diffusion of damaging materials from the blood into the retina,” he says.
“So if you took a tablet in your mouth, the barrier would stop the drug moving from the blood to the retina.”
To overcome this difficulty, the researchers have come up with a system to loosen the tight junctions just enough to let small molecules pass through.
How does it work? You take a specially engineered viral carrier that can make an RNA molecule to block the cell from making claudin-5, an important protein component of the tight junctions, and you inject that virus behind the retina at the back of the eye.
“So you get claudin-5 suppression just at the blood-retina barrier, just where you inject it,” says Campbell.
Dampening down the claudin-5 tweaks the blood-retina barrier so that it lets molecules below a certain size threshold through, but it still excludes much larger invaders such as bacteria, he adds.
Chronic eye conditions such as age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders may respond to the range of low molecular weight drugs that the TCD approach could now put on the guest list into the retina.
And to avoid compromising the barrier when you don’t need to, the virus is also designed to only suppress claudin-5 in the presence of an antibiotic.
In short – put the virus system in once, then give an oral antibiotic to turn it on and open the barrier any time you want to deliver a drug from the blood into the retina.
The researchers have already proven the approach works experimentally, and if approved for clinical use in humans it could offer a potentially safer and more patient-friendly alternative for chronic conditions where current treatments can involve repeated injections of drugs directly into the eye.
“You get a single injection of this humanised virus and then induce the barrier to open and take your drug orally,” says Campbell.
The team, which is led by Prof Pete Humphries, is also developing RNA-based approaches to overcome a similar barrier between the blood and the brain, where opening the gates could improve cancer and injury treatments.
“We are not breaking the blood-brain barrier, that would be an anathema to our endeavours,” says Humphries. “We are just modulating it marginally.”
The research receives funding from the Wellcome Trust, Science Foundation Ireland and Fighting Blindness.