Gene Therapy Gives Monkeys Color Vision

16 September 2009 (All day)

Neitz Laboratory

Now in Technicolor. Squirrel monkey Dalton sees only yellows, grays, and blues before his color blindness treatment (left). A human gene has given him full color vision, revealing a colorful dinner (right).

Squirrel monkeys can now see your true colors, thanks to gene therapy. Researchers have given the colorblind primates full color vision as adults by injecting their eyes with a human gene. The result raises questions about how the brain understands color, and it could eventually lead to gene-therapy treatments for colorblindness and other visual disorders in humans.

In the world of squirrel monkeys, seeing colors is for girls. Whereas some females enjoy full color vision, males of the South American genus see only blues and yellows (see picture). They lack a gene that allows color-sensitive cells in the eye, called cones, to distinguish red and green from gray--the same distinction that confounds most colorblind humans.

Seeking a possible treatment for the human condition, vision scientist Jay Neitz and colleagues at the University of Washington, Seattle, assembled six adult squirrel monkeys, four colorblind males and two female controls. The researchers tested them daily for a year, using a computer program that presented the primates with colorful clumps of dots on a screen of similarly varied gray dots (see video). The results established each monkey's color vision, revealing that the female controls could see colors as a normal human would, while the male monkeys could not distinguish green and red clumps from the gray background. The team then injected the retinas of two of the colorblind monkeys with a virus that introduced the human gene for the red-detecting pigment in cone cells.

The researchers were not optimistic. Unlike the malleable brains of young animals, adult brains are far more rigid and tend to have a harder time rewiring themselves. Many patients blinded in childhood, for example, remain blind when their eyes are repaired in adulthood, because their brains never developed the circuitry for processing what they see.

Twenty weeks after the gene therapy, however, the monkeys began to spot red and green dots in the computer color tests, and soon after they were regularly acing the trials, the researchers report in Nature. "That's when we broke out the champagne," says a still-surprised Neitz. Now, 2 years later, the monkeys remain able to distinguish all colors, almost on par with their female counterparts. Neitz attributes the monkeys' adaptability to the fact that colorblind animals still have color-processing circuitry in their brains. The introduced gene simply gives them the ability to feed new information into the circuitry, "hijacking" a pathway previously used by blues and yellows for reds and greens as well.

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Monkey see, monkey do well. When squirrel monkey Dalton spots colorful dots in a field of gray, he gets a juice reward.

"It's a wonderfully clever experiment ... and an interesting and important discovery," says Bevil Conway, a neuroscientist and visual artist at Wellesley College in Massachusetts. "We think of color vision as requiring a very complicated circuitry. This makes me think it's simpler and more dynamic than that."

"This is one more piece of evidence that the visual system is remarkably plastic," adds Jerry Jacobs, who discovered squirrel monkeys' colorblindness and continues to study color vision at the University of California, Santa Barbara. The real strength of Neitz's study, he notes, is the potential for applying it as treatment for people. Human red-green color blindness is relatively common, afflicting one out of 12 men and one out of 230 women in the United States alone. Neitz's team is now working to make their cure more streamlined and safe for humans; in conjunction with several gene therapy trials already under way, they're also applying their technique to other vision disorders, such as Leber's congenital amaurosis, a hereditary disease that leads to blindness.

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