A gene therapy has enabled people with a rare type of total colour blindness to faintly see red. In a small trial, those who could previously only detect shades of grey went on to distinguish a red object from its darker background.
Ayelet Mckyton at the Hebrew University of Jerusalem, Israel, and her colleagues studied four people with a rare condition called achromatopsia. Affecting about 1 in every 30,000 to 40,000 people, achromatopsia disturbs the eyes’ cone cells, which are otherwise responsible for colour vision.
The participants, of whom three were adults and one was 7 years old, all had a version of the condition caused by a single genetic mutation. The researchers therefore hoped that inserting working copies of the faulty gene into cone cells would provide some degree of colour vision.
To test the idea, they injected a virus carrying the correct gene into the subretinal area, home to cone cells, into one eye of each participant. “The virus then enters the cells with the defective gene and corrects it,” says Mckyton.
No major changes were seen in the participants’ vision in the hours after the procedure, but in the months that followed, some reported seeing shades of grey that “glowed” differently to before the injection, says Mckyton.
After carrying out a series of tests, the researchers found that the participants could see red objects against dark backgrounds in their treated eye, when they couldn’t see the colour at all beforehand.
A previous study that gave gene therapy to sheep used to model human achromatopsia found that the animals developed complete colour vision. In people with the condition, their so-called rod cells, which are highly sensitive to light and provide night-time vision, are active in light, preventing them from otherwise being blind during the day. These cells are inactive during the day in sheep with achromatopsia or people without the condition.
In the trial, the active rod cells may have interfered with the signal produced by the treated cone cells, preventing the participants from seeing in full colour, says Mckyton. They may have been able to see red, however, due to rod cells being particularly insensitive to its wavelength, she says. The rod cells therefore remained inactive when exposed to red and the cone cells’ signals weren’t disturbed.
Mckyton is unsure if the treatment could be modified to treat achromatopsia more effectively. “We don’t know how to silence the rods,” she says. “But I think it’s generally a good thing that these people have active rods, otherwise they would have been blind.”
Gene therapies probably won’t work for other types of colour blindness, as these aren’t generally caused by a single mutation that can be corrected, says Mckyton.
“This is an intriguing study that indicates the complexity of developing a therapy for regaining colour vision,” says Abigail Hackam at the University of Miami, Florida. The participants’ brain circuitry for colour vision may be relatively dormant and hasn’t been sufficiently activated for them to regain colour vision post-injection, hence the limited effectiveness of the therapy, she says.
The participants will be monitored for several years and may then have the injection repeated on their other, untreated eye, says Mckyton.