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Unlike their blind counterparts, treated mice responded to bright light by running around their cages as if to hide. And when placed on a still platform inside a rotating drum with black-and-white stripes, the treated mice followed the moving pattern. By using progressively smaller stripes, the researchers were able to gauge the limit of the mice’s ability to resolve details–it’s about half as good as that of normal mice, as it turns out.

“What was beautiful about this paper was that they were able to restore a behavioral function that was very, very clean and clear,” says Ed Boyden, an assistant professor at the MIT Media Lab, who has pioneered the use of ChR2 for bioengineering in the brain. “This is the first behavioral improvement that people have reported for the use of this gene in the visual system,” says Boyden, who was not involved in the research.

If the technique is adapted to treat blindness in humans, says Roska, the gene will likely be delivered using a virus called AAV. This virus is a common tool for human gene therapy–it was recently used to deliver a cure for an extremely rare type of human blindness–and it has proved safe and effective in a number of clinical trials. By tweaking its coat protein, researchers could potentially adapt AAV to infect only ON bipolar cells, adding another layer of specificity.

Viral delivery could amplify the technique’s effectiveness, says Roska, perhaps improving vision even more. While the technique used to administer the gene in the mouse study only affected about 10 percent of ON bipolar cells, AAV may expand the gene’s reach.

In the future, Roska and his colleagues also plan to address the other half of the bipolar circuit–the OFF bipolar cells. Recently, Boyden and others have been developing a kind of sister technique to ChR2, using a channel protein called halorhodopsin that deactivates cells in response to light. If halorhodopsin were expressed specifically in OFF bipolar cells, that component of the visual circuit could be restored as well. “That would give you kind of a push-pull control of getting information into the brain,” says Boyden.

But Roska’s group is still searching for a gene regulator specific to OFF bipolar cells so that they can target halorhodopsin with adequate specificity. “Although we have the right tool,” he says, “we don’t have the right address.”

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Credit: Botond Roska, Friedrich Miescher Institute for Biomedical Research

Tagged: Biomedicine, vision, proteins

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