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The first successful clinical test of a technique called optogenetics has allowed a 58-year-old man to see for the first time in decades.

The man was able to see with the help of image-enhancing goggles after 40 years of blindness, thanks to an injection of light-sensitive proteins into his retina.

According to a study published by Nature Medicine on May 24, this is the first successful clinical application of optogenetics, a technique in which flashes of light are used to control gene expression and neuron firing.

The study revealed that the technique is widely used in laboratories to probe neural circuitry and is being investigated as a potential treatment for pain, blindness and brain disorders.

The clinical trial, run by the company GenSight Biologics, based in Paris, enrolls people with retinitis pigmentosa — a degenerative disease that kills off the eye’s photoreceptor cells, which are the first step in the visual pathway.

In a healthy retina, photoreceptors detect light and send electrical signals to retinal ganglion cells, which then transmit the signal to the brain.

GenSight’s optogenetic therapy skips the damaged photoreceptor cells entirely by using a virus to deliver light-sensitive bacterial proteins into the RGCs, allowing them to detect images directly.

GenSight is one of several companies developing optogenetics as a treatment for RP and other disorders of the retina.

In March, Nirenberg’s company Bionic Sight announced that four of the five people with RP it had treated with a similar optogenetic therapy and a virtual-reality headset had recovered some level of vision, although the full trial results have not yet been published.

Also, Swiss pharma giant Novartis is developing a therapy based on a different protein that is so light-sensitive that goggles might not be needed. That therapy has not yet entered clinical trials.

The researchers injected the virus into the eye of a man with RP, then waited four months for protein production by the RGCs to stabilise before testing his vision, the Nature Medicine reported.

José-Alain Sahel, an ophthalmologist at the University of Pittsburgh Medical Center in Pennsylvania and leader of the study, says that one of the challenges was regulating the amount and type of light entering the eye, because a healthy retina uses a variety of cells and light-sensitive proteins to see a wide range of light.

“No protein can replicate what the system can do,” he says. So the researchers engineered a set of goggles that captured the visual information around the man and optimised it for detection by the bacterial proteins.

Using a camera, the goggles analyse changes in contrast and brightness and convert them in real-time into what Sahel describes as a ‘starry sky’ of amber-coloured dots. When the light from these dots enters a person’s eye, it activates the proteins and causes the RGCs to send a signal to the brain, which then resolves these patterns into an image.

The trial participant had to train with the goggles for several months before his brain adjusted to interpret the dots correctly. “He was like an experimentalist, a scientist trying to understand what he was seeing and make sense of it,” Sahel says.

Eventually, he was able to make out high-contrast images, including objects on a table and the white stripes in a crosswalk. When the researchers recorded his brain activity, they found that his visual cortex reacted to the image in the same way as it would have if he had normal sight.

The man still can’t see without the goggles, but Sahel says that he wears them for several hours per day and that his vision has continued to improve in the two years since his injection.

Sahel says six other people were injected with the same light-sensitive proteins last year, but the COVID-19 pandemic delayed their training with the goggles.

A neurobiologist at the University of California, John Flannery says the study “is a big step for the field.

“The most important thing is that it seems to be safe and permanent, which is really encouraging.”

Flannery said while the image may never be as good as natural vision, it is exciting that the brain can interpret images accurately.

Other researchers are, however, calling for more studies.

Sheila Nirenberg, a neuroscientist at Weill Cornell Medical College in New York City says she looks forward to seeing whether the other people in the trial, including some who were injected with higher doses of the protein, have similar results.

“It’s interesting, but it’s an N of 1,” she says.

Karl Deisseroth, a neuroscientist at Stanford University in California who co-developed optogenetics as a lab technique, says the study is important because it is the first time that the technique’s effects have been shown in people.

“It will be interesting to try this with more light-sensitive opsins” that might not require goggles, he says. But he expects optogenetics to be most useful as a research tool that leads to therapies, rather than a therapy itself.

“What we hope to see even more of is optogenetics-guided human and clinical studies,” he says.