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Gene therapy adds new dimension of color sensation in primates

Article

In results that challenge conventional models for color vision circuitry, researchers used gene therapy in a dichromatic primate model to add a third photopigment and bring about red-green vision. This successful treatment of adult monkeys with a congenital color vision defect shows that the adult nervous system can respond to newly added sensory input and is encouraging for the possibility of using gene therapy to treat various cone-based vision disorders in human adults, said Katherine Mancuso, MD, of the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee.

In results that challenge conventional models for color vision circuitry, researchers used gene therapy in a dichromatic primate model to add a third photopigment and bring about red-green vision. This successful treatment of adult monkeys with a congenital color vision defect shows that the adult nervous system can respond to newly added sensory input and is encouraging for the possibility of using gene therapy to treat various cone-based vision disorders in human adults, said Katherine Mancuso, MD, of the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee.

In gene therapy experiments using two dichromatic squirrel monkeys (Saimiri sciureus), Dr. Mancuso and colleagues subretinally injected a recombinant adeno-associated virus vector containing an L-opsin gene. The objective was to transduce only a subset of cones. To monitor the effects of the gene therapy, the monkeys were trained prior to treatment to perform a computer-based, adapted version of the Cambridge Colour Test. The monkeys were tested on 16 different hues and repeatedly failed to make the same red-green color discrimination.

"Because you can vary the saturation of each of the colors, it provides a very sensitive method that allows us to quantitatively measure their color vision over time," Dr. Mancuso said.

After treatment, gene expression was first detected at about 9 weeks post injection and become more robust at 20 weeks. Color vision tests indicated that the animals had gained the sensory capacity for red-green color vision, a trait that has persisted for more than a year. Referring to one of her test subjects, a monkey named Sam, Dr. Mancuso that he is now able to see colors that he was previously not able to distinguish from gray and has full trichromatic color vision. The other treated monkey had very similar results.

"Conventional wisdom told us that this treatment shouldn't have been able to work in adult animals, but it did," Dr. Mancuso said.

She theorized that her experiments recapitulated what occurred during the evolution from dichromatic to trichromatic vision in humans' primate ancestors. Trichromacy arose from a random event, adding a third cone type to the retina; the same endpoint was accomplished in her lab with gene therapy.

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