Gene therapy has successfully given colorblind adult monkeys the ability to see red and green, according to a study published this week in Nature, demonstrating a striking plasticity in the adult visual system and providing new hope for treating vision disorders that until now were thought to be incurable in adults.

Monkey taking color vision test Image: Neitz Laboratory

"The surprise is that you can do it with an adult animal," said neuroscientist Jerry Jacobs of the University of California, Santa Barbara, who was not involved in the work. "It's another [piece of] evidence that the visual system is incredibly plastic [and] provides a practical potential for using gene therapy as a way of ameliorating color defects."

Red-green colorblindness is a condition that affects nearly 10 million American men, and a number of women as well. It is caused by the absence of either long (L)- or medium (M)- wavelength sensitive visual photopigments, or the "red" and "green" cones. (The color to which the "red" cones are sensitive is actually more of an orangish-yellow.) The genes coding for these photopigments are found next to each other on the long arm of the X chromosome, one of the most variable areas of the genome. Females with an X chromosome lacking one of these genes are carriers of the condition; their sons who receive the deficient X will be unable to distinguish reds and greens from shades of gray.

In squirrel monkeys, due to slightly different genetics, all males are red-green colorblind. The underlying physiology, however, is the same: Individuals must express both L- and M-cones, as well as the nearly ubiquitous short (S)-wavelength cones, to see the full rainbow.

In this study, visual neuroscientist Jay Neitz of the University of Washington and his colleagues targeted two adult male squirrel monkeys missing the L-opsin gene that codes for the L visual pigment, and are therefore red-green colorblind. They found that 19 weeks after injections of viruses containing the L-opsin gene as well as an enhancer and promoter into both eyes, the monkeys were able to respond to the colors in visual tests.

The general dogma in the field has been that vision develops during a critical period at a very young age, and outside of that window of time, "nothing will happen," Neitz explained. "Here's a different example where everything happens."

Multifocal electroretinogram results, which measure the electrical activity in the eye in response to light, confirmed the spectral sensitivity shift that allowed the monkeys to perceive the new colors.

This result shows that "the visual system was always willing and able to make use of a third pigment," said neuroscientist Joseph Carroll of the Medical College of Wisconsin, who was not involved in the research. "This is the proof of principle that it is possible" to treat vision disorders in adults.

Although color blindness is a relatively mild defect, this type of therapy may shed some light on treating more severe vision disorders, Neitz said. "We're adding light sensitivity to the eye," he said. "Basically all of the incurable eye diseases are ones where people have lost light sensitivity in one way or another."

However, most other blinding diseases involve some kind of degenerative change, Jacobs warned. "The retina is dying for one reason or another." Indeed, in such cases gene therapy may only prove useful if given before retinal degeneration becomes too severe, Carroll agreed, but no matter how it plays out, "this is a game changer. I think in 10 or 15 years we'll look back at this as a really pioneering study [for] applying gene therapy to adult [vision] disorders."


Related stories:

New clues to why we see red
[22nd March 2007]

How birds keep secrets in color
[27th April 2005]

Vision Quest
[10th May 2004]