Males with red-green colorblindness can distinguish the hues after gene therapy, study suggests
Two male squirrel monkeys now see the world in a whole new way — in full color.
Female squirrel monkeys can see in color, but male squirrel monkeys are normally red-green colorblind because they lack pigments in the retina that detect those wavelengths of light. Now, researchers have performed gene therapy that allowed two male squirrel monkeys named Sam and Dalton to produce proteins that detect red light. As soon as the red-light-harvesting protein was made in the monkeys’ eyes, the animals were able to discriminate between red and green spots in color vision tests, Jay Neitz of the University of Washington in Seattle and his collaborators report online September 17 in Nature.
The experiment wasn’t supposed to work, Neitz says. People born with cataracts don’t develop nerve connections that help the brain make sense of messages sent by the eye. If the defect isn’t corrected early, these people remain essentially blind even if their eyes return to full function later. Because there was no reason to assume color vision was different from other types of vision, the team had assumed it would not be possible to reverse the deficit in an adult animal.
Neitz polled experts in the vision field on whether they thought producing photoreceptors in colorblind adult monkeys could give color vision. “Every single person said, ‘absolutely not.’” But the researchers decided to move forward with the experiment to see if they could get the pigment protein to be made in the eye.
Male monkeys lacking the red photoreceptor protein were given injections of a virus carrying a gene for the protein. Levels of the protein slowly rose in some retinal cells. After 20 weeks, Neitz and his colleagues started to see differences in the way Sam and Dalton performed on daily color vision tests. Around that time, protein production levels peaked and the monkeys have maintained stable color vision for two years since treatment.
In the tests, monkeys were shown a panel with a patch of colored dots on a background of gray dots. If the monkeys press the area with the colored dots, the animals get a grape juice reward. Even colorblind monkeys guess correctly about a third of the time, Neitz says.
“Sometimes they get on a streak, so those first couple of days when they were on a streak, we tried not to get too excited,” he says. “But by the end of the week it became clear that this was not random chance.”
Sam and Dalton could consistently pick out red, green, blue and yellow dots from the gray background and discriminate between the colors. Before the gene therapy, they could only discriminate yellow and blue. The speed at which the monkeys learned the new colors indicates that no brain rewiring was required for the feat, unlike that needed to restore other types of vision such as distinguishing objects.
The achievement is causing a stir among vision scientists and may have implications for understanding the evolution of color vision, says Bevil Conway, a neuroscientist at Wellesley College in Massachusetts.
“Somehow the brains of these monkeys are already wired to decode these color signals,” Conway says. That fact raises the possibility that “the evolution of color vision may have required just one genetic switch.”
But, Conway says, there is an important disclaimer. “We have no idea if this would work in humans or that it would be a delightful experience for the people post-surgery.” People who have surgery to repair sight lost in childhood often report that their new vision is confusing and disorienting, he says. Adding color could prove to be similar.
Other scientists who originally thought color vision couldn’t be generated in adult animals are impressed by Neitz’s achievement.
“They certainly have added some color vision,” says Gerald Jacobs, a neuroscientist at the University of California, Santa Barbara. “I find the measurements compelling.”
Still, the monkeys’ actual sensation of color — what it looks like to them — remains a mystery.
“The achievement is technically amazing and conceptually very cool,” says Melissa Saenz, a neuroscientist at Caltech in Pasadena, Calif. But even though the monkeys can discriminate some new wavelengths of light, “there's no evidence that the monkeys perceive a new dimension of color,” she says. For example, the monkeys may now perceive red and green as different shades of yellow and blue, colors the animals already knew.
“If it doesn't involve experiencing new sensations of color, it would not dramatically change the experience of colorblind people if the treatment were applicable to humans,” Saenz says.
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