Focus on a cure for blindness

TCD researchers have developed a gene therapy for mice which could be used to treat diseases that cause blindness in humans

SCIENTISTS in Dublin have developed a treatment that has reversed a form of blindness in mice. Although not yet ready for use in humans, the experiment shows that it may soon be possible to cure some of the most common forms of blindness.

Prof Jane Farrar, of the Smurfit Institute of Genetics at Trinity College Dublin, led the research, which was published last week in the journal, Human Gene Therapy. Other participants in the work included Trinity's Dr Paul Kenna, Prof Peter Humphries and lead scientist, Dr Arpad Palfi.

The technique involved using a harmless virus to deliver a missing gene into the retinas of lab mice who have a form of retinal degeneration, Farrar explains. The mice have no working rod photoreceptor cells because the gene for a substance called rhodopsin is not present.

The rhodopsin gene was inserted into the harmless virus and this in turn was injected into the back of the retina. “We only need a very small amount, about 5,000 times smaller than a teaspoon,” she says.

“We put it into a mouse that does not make normal photoreceptors. When we injected the virus and looked at that mouse eye, several weeks later, we saw photoreceptors that look like healthy photoreceptors,” she says.

The researchers could see that the atrophied cells had been “rescued” and had developed due to the presence of the missing rhodopsin.

Before treatment, the rod cells are present but do not work and are missing related structures around them, known as “outer segments”, that appear similar to a stack of biscuits.

Once the virus had penetrated the cells to insert the gene and rhodopsin began being produced, the cells changed to look like normal cells, Farrar says.

Research fellow Paul Kenna, a clinical opthomologist and surgeon and the director of the research foundation at the Eye and Ear Hospital in Dublin, carried out the procedures on the mice.

Kenna was able to show that the rescued photoreceptor cells responded like normal cells through the use of a test called an electroretinogram. “This is a test used clinically to test for human rod cell function,” Kenna says.

It involves using a flash of light and then reading the electrical response in the retina as the cells return a signal to the brain. Before treatment the retinas in mice without rhodopsin did not respond to the light at all. After treatment however there was a clear signal.

“They generated quite a generous electrical signal, meaning there was a functioning rhodopsin gene working in the retina,” he explains.

Much experimentation remains to be completed, but top-up injections will not be needed, Farrar says. “In principle, a single injection should have a long-term effect.”

This is because rod and cone cells in the retina are actually specialised neurons, the kind of cells which make up the brain. “The retina is actually an accessible part of the brain,” says Farrar.

The study opens up a great many possibilities for the treatment of certain conditions that cause blindness in humans, Farrar says. “Many diseases could be cured in this way.”

These include rhodopsin- linked forms of retinitis pigmentosa, a common progressive blinding disease, and also age-related macular degeneration, one of the most common forms of gradual blindness. “The same technology could be used to treat these diseases.”

The virus used, an adeno- associated virus, causes no human illness and is already being used in other therapies related to vision and blindness.

“The fact that there are treatments involving the same virus should speed up [human] trials,” Farrar says of the work at Trinity. More research remains to be done before this approach could be tried in humans, but she believes this could happen within a few years.

The work was funded by the research charity Fighting Blindness Ireland and by Science Foundation Ireland. “This is patient-led research. They are driving the research forward,” Farrar said of Fighting Blindness Ireland.