October 4, 2023

A team of scientists announced Monday that they partially restored a blind person’s eyesight by building light-trapping proteins in one of their eyes. Their report, published in the journal Nature Medicine, is the first published study describing the successful use of this treatment.

“It’s exciting to see it worked for the first time – even if it only works in one patient and in one eye,” said Ehud Isacoff, a neuroscientist at the University of California at Berkeley who was not involved in the study.

The procedure is far from full view. The volunteer, a 58-year-old man who lives in France, had to wear special protective goggles that allowed him to perceive objects in a narrow field of vision. However, the report’s authors say the study – the result of 13 years of work – is proof of concept for more effective treatments.

“It’s obviously not the end of the road, but it’s an important milestone,” said Dr. José-Alain Sahel, an ophthalmologist who divides his time between the University of Pittsburgh and the Sorbonne in Paris.

Dr. Sahel and other scientists have spent decades trying to find a cure for inherited forms of blindness. These genetic disorders rob the eyes of the essential proteins necessary for vision.

When light enters the eye, it is captured by so-called photoreceptor cells. The photoreceptors then send an electrical signal to their neighbors called ganglion cells that can identify important features such as movement. They then send their own signals to the optic nerve, which delivers the information to the brain.

In previous studies, researchers were able to treat a genetic form of blindness known as congenital liver amaurosis by repairing a faulty gene that would otherwise cause photoreceptors to gradually degenerate.

However, other forms of blindness cannot be treated as easily as their victims lose their photoreceptors completely. “Once the cells are dead, you can’t fix the genetic defect,” said Dr. Sahel.

For these diseases, Dr. Sahel and other researchers experimented with a more radical type of repair. They use gene therapy to convert ganglion cells into new photoreceptor cells, even though they don’t usually capture light.

The scientists use proteins from algae and other microbes that can make every nerve cell sensitive to light.

In the early 2000s, neuroscientists figured out how some of these proteins could be built into the brain cells of mice and other laboratory animals by injecting viruses that carry their genes. The viruses infected certain types of brain cells, which then used the new gene to build light-sensitive channels.

The researchers originally developed this technique, known as optogenetics, to study how the brain works. By introducing a tiny light into the animal’s brain, they can turn a certain type of brain cell on or off with the push of a button. The method enabled them to discover the circuits that underlie many types of behavior.

Dr. Sahel and other researchers wondered if they could use optogenetics to add photosensitive proteins to cells in the retina. After all, retinal cells are also nerves – in other words, an extension of the brain.

For Ed Boyden, a neuroscientist at MIT who pioneered optogenetics, he was surprised to find the use of these proteins to cure blindness. “So far, I’ve thought of optogenetics primarily as a tool for scientists because it’s used by thousands of people to study the brain,” he said. “But if optogenetics proves itself in the clinic, it would be extremely exciting.”

Dr. Sahel and his colleagues realized that Dr. Boyden and others produced optogenetic proteins were not sensitive enough to produce an image from normal light entering the eye. However, the scientists could not shine amplified light into the eye because the glare would destroy the sensitive tissue of the retina.

So the scientists chose an optogenetic protein that is only sensitive to amber light, which is easier on the eye than other colors, and used viruses to deliver these amber proteins to the ganglion cells in the retina.

Next, the researchers invented a special device to convert visual information from the outside world into amber light that could be seen by the ganglion cells. They have developed protective goggles that scan their field of vision thousands of times per second and register every pixel in which the light changes. The goggles then send a pulse of amber light from that pixel into the eye.

The researchers concluded that this strategy can potentially create images in the brain. Our eyes, of course, flit around in tiny movements many times per second. With every jump, many pixels would change the light intensity.

However, it was an open question whether blind people could learn to use this information to recognize objects. “The brain has to learn a new language,” said Botond Roska, an ophthalmologist at the University of Basel and co-author of the new study.

After Dr. Roska, Dr. Sahel and her colleagues had tested their gene therapy and goggles on monkeys, they were ready to try them on humans. Their plan was to inject gene-carrying viruses into one eye of each blind volunteer and then wait several months for the ganglion cells to grow optogenetic proteins. They would then train the volunteers to use the goggles.

Unfortunately, they only managed to train one volunteer before the coronavirus pandemic closed the project. After years of preparing for the study, she was now in limbo.

But then the one volunteer they had trained volunteered. He had been wearing the goggles at home and on walks for seven months. One day he realized that he could see the lines of a zebra crossing.

When the pandemic subsided in France in the summer, scientists managed to get him to their laboratory for further training and testing. They discovered that he could touch a notebook on a table, but had less luck with a smaller box of staples. When the scientists placed either two or three beakers in front of the volunteer, he managed to count them correctly 12 out of 19 times.

During some of the experiments, the volunteer wore a cap with electrodes that could sense brain activity through his scalp. When the goggles sent signals to his retina, they activated parts of the brain that were involved in vision.

“From a scientific point of view, and especially for the blind, this is a great achievement,” said Lucie Pellissier, a neuroscientist at the University of Tours in France who was not involved in the study.

Dr. Sahel and his colleagues started a company called GenSight to take their technology through clinical trials in hopes of getting regulatory approval. You are not alone. Dr. Isacoff and his colleagues started a similar company called Vedere Bio, which was acquired by Novartis last October.

It will take a lot more positive results from clinical trials before optogenetics can become the standard treatment for some forms of blindness. Currently, Dr. Sahel and his colleagues train the other volunteers to train, test higher doses of the virus and upgrade their safety glasses to thin glasses that are more comfortable and at the same time provide more information to the retina.

Dr. Isacoff and his colleagues have carried out their own experiments which open up the possibility that other optogenetic proteins could make retinal cells sensitive enough to detect light without protective goggles. “I think it’s going to work pretty well,” he said.

During the whole time that Dr. Put Sahel into his own system, he hesitated to guess how much it could improve. “Until a patient tells you what they see, you really can’t predict anything,” he said.