Two colour-blind monkeys nicknamed Dalton and Sam have been 鈥渃ured鈥� through gene therapy.
The breakthrough could be a prelude to new gene treatments for human vision disorders that currently result in blindness. And because the treated monkeys were 鈥渕iddle aged鈥�, it challenges the assumption that gene therapies cannot work in adults because their brain connections are too set in their ways to change beneficially.
A human gene injected into the monkeys鈥� eyes enabled them for the first time to produce 鈥渓ong-wavelength opsin鈥� 鈥� the pigment sensitive to red and green light. 鈥淭hat gave them a retina like that of a normal person with full colour vision,鈥� says at the University of Washington in Seattle.
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The team used squirrel monkeys because the males are known to be colour-blind, whereas females have full colour vision. Males do have a full set of colour-sensing 鈥渃one鈥� cells in their eyes, but they only make pigments for detecting blue and yellow light, making them blind to red and green.
Monkey see, monkey do
To try correcting the condition, the researchers used injections of a harmless cold-like virus to deliver the human gene into layers of cells just below the retina.
By attaching the gene to a 鈥渟witch鈥� activated only in specific cone cells of the retina, the researchers restricted production of the pigment to some, but not all of the available cone cells, so that some would continue detecting blue and yellow.
After about 20 weeks, visual tests on the monkeys demonstrated that they had full colour vision. Neitz and his colleagues could tell because prior to the therapy, they had trained Dalton and Sam with rewards to pick out yellow or blue dots on a grey background. To win their reward, they pressed a button with their noses when they could see the dots.
Before treatment, they were blind to red or green dots on the grey background, but afterwards they began pressing the button, revealing that they could distinguish the red and green dots, too.
Avoiding burn-out
Although gene therapy may be too risky to attempt as a cure for colour-blindness, Neitz says the success of the therapy demonstrates the potential of the technique to treat more serious conditions. Already, he and his collaborators have begun a trial to treat a condition called Leber congenital amaurosis (LCA), a form of blindness that affects children.
Youngsters with the condition are unable to make functional copies of an enzyme which recycles 11-cis-retinal, a component of vitamin A vital to the structure of all working pigments. Without this, they have rod cells in their eyes that don鈥檛 work at all, and cones that work very poorly and which burn out by early adulthood.
Neitz and his partners have begun a trial in adults to restore working copies of the gene that makes the necessary enzyme in adults who鈥檝e already lost much of their function. If the treatment proves safe, it may then be tried out in children under 10 whose rods and cones are less withered than those in affected adults.
Plastic brain
Just recently, a similar trial in children began in the UK following the success of earlier trials in adults. 鈥淣ow we鈥檝e started to treat children,鈥� says of University College London, and head of the group conducting the study.
Ali says that the results from the monkey trial have given a tremendous boost to everyone developing gene therapies to treat vision disorders. 鈥淭he results are remarkable,鈥� he says.
Most striking, says Ali, is the discovery that the brains and retinas of the adult monkeys weren鈥檛 too 鈥渉ard-wired鈥� or fixed to respond to the treatment. 鈥淲hat鈥檚 so exciting about this study is that is demonstrates there鈥檚 more plasticity in the brain and cone cells than we thought,鈥� says Ali. 鈥淚t forces us to reconsider our assumptions, and opens up more possibilities than we thought for treating blindness.鈥�
See the future
Ali says that there are about 100 inherited disorders of vision that might be amenable to gene therapy. Both he and Neitz think that one disorder that could possibly be treated is achromatopsia, in which people can鈥檛 see any colour at all.
But like Neitz, Ali thinks that gene therapy might currently be too risky to treat ordinary colour blindness. 鈥淚 have it myself, and would not consider gene therapy as something that鈥檚 warranted to treat it,鈥� he said. 鈥淚 think the risks outweigh any benefit.鈥�
One very speculative and futuristic possibility is that of using gene therapy to equip humans to see ranges of light invisible to them at present, such as ultraviolet or infrared light. Some birds and reptiles can sense UV light, for example, and some fish can sense wavelengths approaching those in the infrared. 鈥淚 wouldn鈥檛 rule it out completely, but it鈥檚 very futuristic,鈥� says Neitz.
Journal reference: (in press)
