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Gene Therapy Treats Red-Green Colorblindness In Adult Monkeys

A potential cure for red-green colorblindness is one step closer to reality following research from the University of Washington. An article in the October 8th issue of Nature reported that scientists were able to successfully treat red-green colorblind adult squirrel monkeys using gene therapy.

Red-green colorblindness, which affects 1 in 12 men and 1 in 230 women, makes day-to-day living more difficult for those who suffer from it. Routine decisions, such as choosing clothes that match or determining if meat is cooked, are tremendously more difficult. Even some professions may be off-limits to those who cannot properly distinguish colors.

Human clinical trials of the new treatment are being planned, but much work remains before they can begin. For instance, researchers are working to find safer and more effective methods for delivering the gene therapy. Additionally, an industrial partner would likely be necessary to help offset the financial costs. For Jay Neitz, UW ophthalmology professor and principal investigator behind the current research, curing red-green colorblindness would be just the first step toward other new treatments for vision disorders.

Squirrel monkeys are a useful model for study because the males are naturally red-green colorblind. This defect is due to the lack of an essential color-sensing gene, which causes the monkeys to "see” gray instead of red or green. However, the monkeys are still able to correctly process the colors blue and yellow.

Exploiting this visual deficiency, researchers trained the monkeys to play a game in which they responded to various colors of light. Correct responses were rewarded with juice, while incorrect responses were punished with an obnoxious noise and a three-second "penalty time.” Prior to gene therapy, the monkeys could only respond to blue or yellow light and were completely incapable of sensing red or green.

According to lead author Katherine Mancuso of the UW ophthalmology department, if the monkeys were not satisfied by frequent blue or yellow lights (and hence, frequent treats), they quit the game in protest.

The monkeys were then subjected to gene therapy. This therapy involved placing the human version of the missing color-sensing gene into a modified virus and then injecting these special viruses behind the monkeys' retinas. Once inside the retina, the viruses were able to deliver the color-sensing gene directly into the cells responsible for detecting color. This technique was described as "remarkable” by Robert Shapley, a scientist unaffiliated with the research from NYU's Center for Neural Science.

Following gene therapy, the monkeys were able to respond to all colors of light. While it is unclear if the monkeys properly perceive their new colors as "red” and "green,” at the very least it does appear that the monkeys are able to see something that they were previously unable to see.

Approximately three years have passed since the monkeys underwent this therapy. According to Mancuso, the monkeys are still able to respond to all colors of light, with no observable side effects.

Besides therapeutic implications, this research challenges the conventional wisdom that sensory input signals (such as colors and sound) must be present from an early age in order for the adult brain to properly process them. This belief is based on previous experiments which demonstrated that eyes deprived of visual stimuli at a young age never acquired visual ability. Therefore, it was believed by many scientists that colorblind monkeys, after reaching adulthood, would never be able to detect the colors red and green.

The success of this therapy, therefore, raises fundamental questions about neural development and sensory perception. More importantly, it opens the door to treatments previously thought impossible.

Alex B. Berezow is a microbiology Ph.D. candidate at the University of Washington.

Image:

"Dalton” the monkey enjoys his new colors at a fruity feast. The image on the left has been altered to simulate what a red-green colorblind monkey (or person) would see. Photo: Neitz Lab


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