Color blindness corrected by gene therapy
Treated monkeys can now see in technicolour.
Researchers have used gene therapy to restore colour vision in two adult monkeys that have been unable to distinguish between red and green hues since birth — raising the hope of curing colour blindness and other visual disorders in humans.
"This is a truly amazing study," says András Komáromy, a vision researcher and veterinary ophthalmologist at the University of Pennsylvania in Philadelphia, who was not involved in the research. "If we can target gene expression specifically to cones [in humans] then this has a tremendous implication."
About 1 in 12 men lack either the red- or the green-sensitive photoreceptor proteins that are normally present in the colour-sensing cells, or cones, of the retina, and so have red–green colour blindness. A similar condition affects all male squirrel monkeys (Saimiri sciureus), which naturally see the world in just two tones. The colour blindness in the monkeys arises because full colour vision requires two versions of the opsin gene, which is carried on the X chromosome. One version codes for a red-detecting photoreceptor, the other for a green-detecting photoreceptor. As male monkeys have only one X chromosome, they carry only one version of the gene and are inevitably red–green colour blind. A similar deficiency accounts for the most common form of dichromatic color blindness in humans. Fewer female monkeys suffer from the condition as they have two X chromosomes, and often carry both versions of the opsin gene.
"Here is an animal that is a perfect model for the human condition," says Jay Neitz of the University of Washington in Seattle, a member of the team that carried out the experiment.
Neitz and his colleagues introduced the human form of the red-detecting opsin gene into a viral vector, and injected the virus behind the retina of two male squirrel monkeys — one named Dalton in honour of the British chemist, John Dalton, who was the first to describe his own colour blindness in 1794, and the other named Sam. The researchers then assessed the monkeys' ability to find coloured patches of dots on a background of grey dots by training them to touch coloured patches on a screen with their heads, and then rewarding them with grape juice. The test is a modified version of the standard 'Cambridge Colour Test' where people must identify numbers or other specific patterns in a field of coloured dots.
After 20 weeks, the monkeys' colour skills improved dramatically, indicating that Dalton and Sam had acquired the ability to see in three shades (see video). Both monkeys have retained this skill for more than two years with no apparent side effects, the researchers report in Nature1.
Adding the missing gene was sufficient to restore full colour vision without further rewiring of the brain even though the monkeys had been colour blind since birth. "There is this plasticity still in the brain and it is possible to treat cone defects with gene therapy," says Alexander Smith, a molecular biologist and vision researcher at University College London, who did not contribute to the study.
"It doesn't seem like new neural connections have to be formed," says Komáromy. "You can add an additional cone opsin pigment and the neural circuitry and visual pathways can deal with it."
Three human gene therapy trials are currently under way for loss of sight due to serious degeneration of the retina. These phase I safety studies injected a similar type of virus vector (but carrying a different gene) behind the retina as in the monkeys, and people treated have shown no serious adverse effects more than a year after, with some participants reporting marked improvements in vision2. These first human trials — which repair rods, a different type of photoreceptor cell — can be seen as a safety benchmark for any future treatment of cone diseases and colour blindness in humans, says Neitz.
"The biggest issue is that people who are colour blind have very good vision," Neitz says. "So before people are going to want to treat colour blindness you're going to want to ensure that this is completely safe, and that's going to take some work."
- Mancuso, K. et al. Nature advanced online publication, doi:10.1038/nature08401 (2009).
- Cideciyan, A. V. et al. N. Engl. J. Med. 361, 725-727 (2009).