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Squirrel monkeys, which are naturally red-green color-blind, can attain humanlike color vision when injected with the gene for a human photoreceptor. The research, performed in adult animals, suggests that the visual system is much more flexible than previously thought–the monkeys quickly learned to use the new sensory information. Researchers hope these results will also hold true for humans afflicted with color blindness and other visual disorders, expanding the range of blinding diseases that might be treated with gene therapy.

“The core observation here is that the animal can use this extra input on such a rapid timescale and make decisions with it,” says Jeremy Nathans, a neuroscientist at Johns Hopkins University in Baltimore, who was not involved in the study. “That’s incredibly cool.”

“This is an amazing step forward in terms of our ability to modify the retina with genetic engineering,” says David Williams, director of the Center for Visual Science at the University of Rochester in New York, who was not involved in the study.

Normal vision in squirrel monkeys is almost identical to red-green colorblindness in humans, making the monkeys excellent subjects for studying the disorder. Most people have three types of color photoreceptors–red, green, and blue–which allow them to see the full spectrum of colors. People with red-green color blindness, a genetic disorder that affects about 5 percent of men and a much smaller percentage of women, lack the light-sensitive protein for either red or green wavelengths of light. Because they have only two color photoreceptors, their color vision is limited–they can’t distinguish a red X on a green background, for example.

In the new study, published today in Nature, scientists from the University of Washington in Seattle injected the gene for the human version of the red photopigment directly into two animals’ eyes, near the retina. The gene, which sits inside a harmless virus often used for gene therapy, is engineered so that it only becomes active in a subset of green photoreceptors. It begins producing the red pigment protein about nine to 20 weeks after injection, transforming that cell into one that responds to the color red.

Researchers screened the monkeys before and after the treatment, using a test very similar to the one used to assess color blindness in people. Colored shapes were embedded in a background of a different color, and the monkeys touched the screen where they saw the shape. The researchers found that the animals’ color vision changed dramatically after the treatment. “Human color vision is very good; you only need a tiny bit of red tint to distinguish two shades,” says Jay Neitz, one of the authors of the study. “[The] cured animals are not quite as good as other [types of] monkeys with normal color vision, but they are close.”

Both animals described in the study have also retained their new tricolor sensory capacity for more than two years. And neither has shown harmful side effects, such as an immune reaction to the foreign protein. The researchers have since treated four additional animals, with no signs of complications. “The results are quite compelling,” says Gerald Jacobson, a neuroscientist at the University of California, Santa Barbara, who was not involved in the study. “There is the potential to do the same for humans.”

Gene-therapy trials are already under way for a more severe visual impairment, called Leber congenital amaurosis, in which an abnormal protein in sufferers’ photoreceptors severely impairs their sensitivity to light. Whether this research should be converted into a treatment for human color blindness is likely to be controversial. “I think it would be a poor use of medical technology when there are so many more serious problems,” says Nathans. “Color-vision variation is one of the kinds of variations that make life more interesting. One may think of it as a deficiency, but color-blind people are also better at some things, such as breaking through camouflage.” They may also have slightly improved acuity, he says.

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Credits: Neitz Laboratory
Video by Neitz Laboratory

Tagged: Biomedicine, blindness, neurology, vision, genetic therapy, primate

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