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Biomedicine

Color-Blind Monkeys Get Full Color Vision

Gene therapy can transform the visual system, even in adults.

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.

Color scheme: To assess color vision in monkeys after gene therapy treatment, scientists adapted a version of a test commonly used to screen colorblind people. If the monkey correctly identifies the red spot on a grey background by touching it on the screen, it gets a juice reward.

“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.

Living color: The image on the left is digitally altered to simulate what the scene would look like to a person (or monkey) with red-green color blindness.

However, both Nietz and Jacobson say they frequently receive calls from color-blind people searching for cures, and they hope the research can eventually be used in humans.

“It seems a trivial defect for those of us who are not color-blind, but it does close a lot of avenues,” says Jacobson. People who are color-blind can’t become commercial pilots, police officers, or firefighters, for example. “People tell me every day how they feel that they miss out because they don’t have normal color vision,” says Neitz. “You obviously don’t want to risk other aspects of vision, but I think this could get to a point where this could be done relatively without risk.”

The findings challenge existing notions about the visual system, which was thought to be hardwired early in development. This is supported, for instance, by the fact that cats deprived of vision in one eye early in life never gain normal use of that eye. “People had explored visual plasticity and development using deprivation in a lot of different ways,” says Neitz. “But no one has been able to explore it by adding something that wasn’t there.”

That flexibility is also important for clinical applications of the technology. The fact that adult monkeys could use their novel sensory information suggests that corrective gene therapies for color blindness need not be delivered early in development, as some had feared. However, it’s not yet clear whether color vision will be a unique example of plasticity in the adult visual system, or one of many.

Researchers hope the findings will prove applicable to other retinal diseases. Hundreds of mutations have already been identified that are linked to defects in the photoreceptors and other retinal cells, leading to diseases such as retinitis pigmentosa, a degenerative disease that can lead to blindness. However, unlike color blindness, in which the visual system is intact, save for the missing photopigment, many of these diseases trigger damage to the photoreceptor cells. “I think it’s hard to know in what way it will extrapolate to more serious blinding disorders that involve more serious degeneration of retina,” says Nathans.

The research also raises the possibility of adding new functionality to the visual system, which might be of particular interest to the military. “You might be able to take people with normal vision and give them a pigment for infrared,” says Williams. “I’m sure a lot of soldiers would like to have their infrared camera built right into the retina.”

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