Our nerves’ electrical impulses are created by a class of proteins called ion channels, which let ions flow into and out of cells. But controlling the flow of ions has uses that go well beyond creating nerve impulses, and there are many other channels made by cells—and even some made by bacteria and other organisms that don’t have nerves.
Scientists have discovered channels that only allow ions to flow after being triggered by light of specific wavelengths. When placed back into nerve cells, the channels turned out to be useful, as they allowed researchers to activate nerves using nothing but light. This discovery created an entire field of research—optogenetics—which has demonstrated that even complicated behaviors like socializing can be controlled with light.
But light-activated nerve activity is also part of normal biology, in the form of our eyes. The development of channels as a research tool has raised the prospect of using them to treat failing vision. In an important proof of concept, researchers have now used a light-sensitive channel and some specialized goggles to allow someone who is otherwise blind to locate objects.
The person who volunteered for the study suffers from retinitis pigmentosa, a genetic disease that causes the degeneration of the retina. At best, the subject can distinguish whether there’s light in his environment.
To try to restore the participant’s vision, a research team in France engineered a virus to carry a light-sensitive channel and a fluorescent protein so that the researchers could determine which cells the virus infected. The researchers injected the virus into the volunteer’s eye, where some of the infected cells included the nerve cells that carry information through the optic nerve and into the brain. While those cells aren’t the same as the specialized cells that typically sense light, the virus essentially converted the cells into light-sensitive nerve cells.
But the channel isn’t sensitive to many wavelengths of light (it primarily picks up yellowish colors), so it would only capture a small amount of potential visual information on its own. That’s where the goggles come in—they capture the full spectrum of light and convert it into monochromatic light at the amber color that the channel is sensitive to. The goggles broadcast the visual information into the virus-infected eye in real time. If the channels successfully pick that information up, they will restore some sight to the volunteer.
For a while, that “if” was looking like a considerable one. It took roughly a year, including seven months of vision training, for the volunteer to start noticing any visual information. The fact that the person went to the training for all that time is a testament to his commitment to the project.
Once some degree of visual perception was restored, the researchers had the volunteer perform some basic tasks, like locating an object on a table. They compared three conditions: both eyes open without goggles; the treated eye open without goggles; and having the system work as intended, with the goggles on and the treated eye open. The participant was unable to locate anything without the system functioning. But when the goggles were stimulating his genetically engineered eye, he had a 92 percent success rate. When multiple objects were present, he was able to count them over 60 percent of the time.
Testing confirmed that the system restored neural activity to the appropriate parts of the brain for vision.
More to come
Restoring object discrimination is a significant step, even if it falls far short of complete vision restoration. But there are some ways to improve the performance of the system. One obvious method would be to genetically engineer cells in the participant’s second eye. It should also be possible to re-infect the first eye in the hope of increasing the number of light-responsive cells.
Finally, the authors suggest using the virus’s fluorescent tag, which will let them identify where light-sensitive cells are located. This could allow the researchers to tailor the goggles to project more information onto the most responsive parts of the eye. Finally, it’s possible that further training will restore more functional activity to the volunteer’s visual system.
One important caveat is that the volunteer had normal vision for many years, enabling the maturation of a functional vision processing system in his brain. So the system was in essence plugging in to a visual network that already worked. The same may not be true for someone who is born without sight.
Regardless of the system’s limitations, it’s impressive that it works at all. A few decades ago, both the goggles and the genetic engineering arms of the system would have been considered science fiction.
Nature Medicine, 2021. DOI: 10.1038/s41591-021-01351-4 (About DOIs).