Scientists partially restore blind man's vision with breakthrough gene therapy

The case marks the first time sight has been partially restored using optogenetics, a type of biological research aimed at controlling nerve cells via light.

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Retinitis pigmentosa, an inherited eye disease, can cause total blindness.

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Scientists have restored useful sight to a 58-year-old man with the inherited eye disease retinitis pigmentosa by injecting genetically engineered viruses into his eye. The man, who had been blind for decades, was able to see small objects like a staple box, a tumbler or a notebook when wearing a specialized pair of goggles. 

The breakthrough is described in a paper published in the journal Nature Medicine on Monday. It relies on optogenetics, a fledgling area of biological research aimed at controlling nerve cells via light.  

"These are very exciting results," says Raymond Wong, a stem cell biologist at the University of Melbourne developing treatments for eye diseases who was not affiliated with the study. 

While the potential therapeutic benefits are enormous, Wong notes the technique has, so far, only been used in one patient. It forms part of an ongoing clinical trial to test the safety and tolerability of the gene therapy. Continued testing and refinement could see the technique help blind patients navigate day-to-day tasks more effectively. 

How did they do it? By re-engineering cells of the eye to make them more sensitive to light. 

The eye's computer

You're reading this article on your mobile device or your computer screen because of the complex decoding performed by your retina. The retina is like a "biological computer at the back of your eye," according to Botond Roska, a biomedical researcher at the University of Basel and author on the new study.

Like onions, this computer has layers. Light filters in through the eye and interacts with specialized photoreceptor cells at the bottom layer of the computer, known as rods and cones. These pass signals on to another specialized cell known as a retinal ganglion cell, which sits at the top layer of this computer.

But in the disease retinitis pigmentosa, the bottom layer is scrambled. Genetic mutations cause the rods and cones to function incorrectly or die off. There are dozens of different mutations which can lead to retinitis pigmentosa. The disease affects up to 1 in 4,000 people worldwide, according to the National Institutes of Health. In many cases, this results in a patient with tunnel vision and eventually most patients lose their sight.

That was the case for the 58-year-old patient at the centre of the new study. "His retina was unable to detect any significant signal," said José-Alain Sahel, an ophthalmologist at the University of Pittsburgh and first author of the study.

Although the patient's photoreceptor cells are not functional, his retinal ganglion cells are. These cells usually receive the signal from rods and cones and pass it onto the brain. It's these cells which the researchers targeted with their optogenetic therapy.

"Optogenetics is the science of taking non-light sensitive cells and introducing genes to them that make them light sensitive," says Philip Lewis, a biomedical engineer at Monash University.

The team created a viral vector, similar to the one used to deliver COVID-19 vaccines, which delivers a gene into the ganglion cells that is sensitive to amber, or red, light. Once the gene is delivered into the eye, it makes a specific light-sensing protein known as channelrhodopsin, which is usually made by algae and helps the organism search for sunlight. 

"They've kind of re-engineered the upper layer of the retina to become the new light-sensitive layer," Lewis notes.

One vision

To restore vision, the patient needs to wear a pair of goggles which turns the incoming light into monochromatic images and projects them, real-time, onto the re-engineered cells in the retina. "There is no delay in the process," notes Roska.

The goggles are key and they act kind of like the non-functional rods and cones. Without wearing the goggles, the patient is totally blind. 

After the injection, the man did not notice significant changes in his vision for a number of months. Then, "spontaneously," he began to report that he was able to see the white stripes of a crosswalk while wearing the goggles, according to Sahel. 

The patient underwent several tests in the laboratory. The team released two videos showing the patient trying to locate large items, like a notebook, and smaller items, like tumblers with the goggles on and off. They also showed the visual system in the brain is activated during the experiments by attaching a device that measures brain waves.

Lewis notes the improvement in visual function is quite localized and the patient has to scan around to find the objects, which may be related to how the gene therapy was taken up in the retina. It could be that, closer to the injection site, there's better uptake and so those ganglion cells are responding much better than other regions. Fortunately, the improvement in vision persisted for almost two years, up to 20 months after injection.

Roska tempered the expectations further in a press conference last week, noting the current device would not allow a patient to see a face or read a book, however, because the resolution is not high enough. 

"Although this treatment didn't restore the patient's vision to a normal level, restoration of some basic levels of vision could help blind patients navigate day-to-day task and greatly improve their quality of life," says Wong.   

The scientists note their competing interests, with lead author Sahel declaring a financial interest in GenSight Biologics, which has developed the methodology. Roska serves on the company's advisory board.    

See the future

The study only features a single patient because the pandemic derailed the research team's ability to train and test other people enrolled in the clinical trial. 

"They are telling us what they are seeing and they are telling us how they are using their restored vision," says Sahel. "The patients are really partners, more than ever, in trials."

As the pandemic begins to wane, the researchers are hopeful they can start training other patients enrolled in the trial and assessing how the goggles help. The estimated completion date is late 2025.

Beyond restoring vision to those suffering from retinitis pigmentosa, optogenetics is already revolutionizing medical science and, according to Lewis, "its full potential is really still being explored."
Scientists have tried to coax nerve cells to activate or deactivate using electrical stimulation for decades. But electrical stimulation isn't quite controlled enough. It's like trying to control a lightning bolt to the brain. They stimulate an area, but not specific cells. 

With optogenetics, researchers can genetically engineer specific nerve cells to respond to light stimulation. This provides more fine control over the cell's activity and allows researchers to study the brain with better accuracy, too. The precision is critical. In animal models of Parkinson's disease, scientists have been able to regulate motor behaviours using the technique. Altering the specific activity of nerve cells with light could provide a therapeutic strategy to combat the disease.

"It's clear that light has a huge part to play in the future of healthcare and treatment," Lewis says.