September 28, 2009

Gene Therapy Corrects Monkey Color Blindness

Monkey ponders computer screen with cluster of red dots among gray ones Monkey taking the color vision test. Neitz lab

Researchers used gene therapy to cure red-green color blindness in adult monkeys. The accomplishment is an important step toward developing gene therapy treatments for eye conditions in humans.

The retina, a light-sensitive tissue at the back of the eye, contains light receptor cells called rods and cones. Cones allow us to see in bright light and provide our color vision. Primates can have 3 types of cones, each containing a special pigment (a photopigment called opsin) that is most sensitive to a particular wavelength of light. All 3 types of cones are needed for the brain to process full color vision.

When an individual has only 1 or 2 types of cones that are fully functional, they are considered color blind, meaning they can't distinguish certain colors. The inability to perceive red or green is the most common form of color blindness—and the most common single-gene genetic disorder in humans. It's caused by mutations in either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments. In addition to causing day-to-day problems—like not being able to tell when you're getting sunburned—severe red-green color blindness can exclude you from certain jobs.

A team of researchers led by Dr. Jay Neitz at the University of Washington set out to see if it's possible to cure red-green color blindness in adults. Even if the eyes could be altered to detect another color, it was unclear whether the adult brain would be able to perceive the new wavelengths.

The researchers used squirrel monkeys as a model. The genes causing red-green color blindness, in both people and monkeys, are on the X chromosome, one of the 2 sex chromosomes. Males have only one X chromosome, so one altered copy of the gene can cause the condition, accounting for higher rates in males. Male squirrel monkeys have it even worse than human males: while 1 in 12 men are unable to distinguish between certain colors, all male squirrel monkeys are red-green color blind.

In work supported by NIH's National Eye Institute (NEI), the scientists used subretinal injections to deliver the human L-opsin gene to the retinal photoreceptor layer of 2 monkeys missing the L-opsin gene. Prior to treatment, the monkeys were trained to touch the location of a colored patch hidden among gray dots in a computerized test. Similar to color-blind humans, the monkeys couldn't distinguish red or green before treatment.

Weeks after treatment, the monkeys passed the test easily for all colors, the scientists reported in the online edition of Nature on September 16, 2009. The monkeys could see colors they never could before, demonstrating that the adult nervous system is capable of responding to newly added sensory input.

These results echo recent successes using gene therapy to treat people with Leber congenital amaurosis, an inherited retinal disease that causes severe visual impairment in infancy or early childhood. Taken together, these encouraging results could open the way to treatments for a broad range of eye diseases.

—by Harrison Wein, Ph.D.

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