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The optogenetics approach is conceptually similar to the retinal prosthesis, in which implanted electrodes stimulate the retina in response to light captured by a camera. (One such device was recently approved for clinical use in Europe.) But researchers say that restoring light sensitivity to individual retinal cells should enable more fine-grained vision than direct electrical stimulation, which activates many cells simultaneously. “Although the retina is a fairly thin and small piece of brain tissue, it is extremely complex,” says Horsager. “If we are going to interface with tissue, we want to do it in a circuit-specific and precise way.”

In a water maze test in which the correct direction to swim was illuminated with light, the treated animals found the escape route much more quickly than their untreated counterparts. In very bright light, they performed almost as well as normal mice. The research was published online last week in the journal Molecular Therapy.

While the findings are promising, it’s not yet clear at what resolution the animals can see. The task requires general sensing of light, rather than fine-grained detection. Horsager predicts that a human patient given a similar treatment “would be able to walk outdoors and hopefully sense light and navigate the environment to some degree.”

The researchers plan to tinker with the therapy further before moving into clinical studies. They are exploring other proteins that might provide greater light sensitivity, as well as proteins that would turn off activity in another subset of cells in the retina. The ability to turn some cells on and others off in response to light would theoretically orchestrate a response that is more like that of the normally functioning retina. Because light signals undergo significant processing in the retinal circuits before being transmitted to the brain, the more closely scientists can mimic the activity in the intact retina, the better the resulting vision is likely to be.

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Credit: Mehdi Doroudchi
Video by Brittany Sauser, Alan Horsager's Lab at USC, and the McGovern Institute for Brain Research at MIT, edited by JR Rost

Tagged: Biomedicine, blindness, optogenetics, retinitis pigmentosa, channelrhodospin

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