Darkness is slowly declining for people with retinitis pigmentosa (RP), a degenerative eye disease that affects 2 million people worldwide. The condition is typically diagnosed in childhood or adolescence, but can take until middle age before a person’s vision has deteriorated severely enough to be completely or effectively blind. When the lights finally go out, however, they stay out.
Or so things were before. In a advanced study published today in Nature Medicine, The researchers report a relatively simple but remarkably effective way to restore partial vision to RP-one patients who, with further study, may soon have wide application.
The key lies in the rod-shaped photoreceptors that govern primarily peripheral vision and the cone-shaped receptors that give us our central view of the world. In people with RP, mutations in more than 70 genes cause a slow deterioration of the veins, leading to tunnel vision, and later cones, leading to blindness. Light still flows into the eye through the unaffected lens, and that light could also make its way to the brain through the optic nerve. But the retina, which lies between the two, no longer works.
A team of researchers, led by Dr. José-Alain Sahel, a professor of ophthalmology at the Sorbonne University and the University of Pittsburgh, thought they might have a way to bring the retina back into play: ChrimsonR, a protein that opens electrical channels in neurons and makes them reactive to light. The trick was to find a way to supply the protein — and the answer was to genetically manipulate an innocuous adenovirus to carry ChrimsonR; the virus was then injected into the fluid-filled part of the eye behind the lens.
“The ChrimsonR sparks electrical activity,” says Sahel. “It transforms cells and makes them able to absorb light, even if it takes a little — about four months — for the cells to take the virus and proteins with them.”
Studies of non-human primates have shown that the technique did not harm the eye, and it also helped researchers establish the correct dose of Chrimson4 to sensitize retinal cells. For the human trial, Sahel and his team worked with a 58-year-old man who had been diagnosed with RP 40 years earlier and whose vision was limited to a rudimentary perception of light. They treated the poorer functioning of their two eyes – to save the most healthy margin if something went wrong with the experiment – and injected them with a single dose of the altered virus.
Assuming the experiment worked, the next steps will not be nearly as simple as waiting the required four months or so until the man’s vision has simply returned to the treated eye. ChrimsonR is not remote enough to re-establish the exquisitely complex interaction of canes and cones that give healthy eyes their rich, colorful, three-dimensional view of the world. Rather, it sensitizes cells to the most in the amber spectrum, making shapes and shadows discernible at that color frequency. In addition, a healthy retina reacts in real time to the amount and intensity of light that strikes it, becoming more reactive in low light conditions and less reactive in strong light, to prevent damage to retinal cells. To see everything through the treated eye, the patient needs to put on a pair of glasses that shift the incoming light into the amber spectrum and adjust it to a safe intensity.
“The eye needs a lot of light, but there is a danger that it could be a toxic level,” says Sahel. “Without glasses it could be like the patient looking directly into the sun.”
While waiting for ChrimsonR to take effect, members of the Sahel team worked with the patient, training him with eyeglasses and performing tests to see if he could distinguish objects placed on a table, pointing them out, counting, and take them. Over repeated tests, there was no result – until finally, as Sahel recalls, he received a call from one of his team members with a simple message: “See.”
At the time around the four-month mark, the subject has begun to achieve remarkable results on all laboratory tests. And in the months following this discovery, he became able to navigate his world in new ways: he could detect the crossing at an intersection and count the number of white stripes demarcating it; perceives objects such as a plate, a cup and a telephone; spot a piece of furniture in a room and see a door in a corridor. “It can also,” adds Sahel, “reveal where people are.”
Sahel believes the results will be lasting, or even close to permanent. “We thought this could last at least 10 years or it could be for life,” he says. “If not, we can always go back and re-inject.”
As for whether the treatment is ready for practical application beyond a patient, Sahel says the answer is “a small yes and a big no.” The downside is that the work was just a feasibility study (but by any measure, it succeeded spectacularly). The big no is that much more research needs to be conducted to learn more about dosing levels, to improve both the glasses and the patients who are trained to use them, and to understand when in a person’s RP course. it’s the right time to start treatment — Sahel notes that for now, at least the procedure is only for people with very advanced diseases. “People with RP can maintain the central vision for several years,” he says. “You always have to weigh the benefit versus the risk.”