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Blind mice see the light

Protein from algae could one day be used in treatments for blindness.

Bright lights make treated 'blind' mice leap into action. Credit: Punchstock

Blind mice have been made to sense light by inserting a protein derived from algae into their eyes. A similar method could one day be used to treat certain forms of blindness in humans, the researchers hope.

The light-sensitive protein, called channelrhodopsin-2 (ChR2), is used by algae to sense light for photosynthesis. Some researchers are interested in using these light-sensitive proteins to replace damaged or missing photoreceptors in animals' eyes. This happens in several human conditions, including the late stages of a relatively common form of blindness: age-related macular degeneration. At present, there are no cures for such patients, though treatments including gene therapy and laser surgery are being tested.

The algae protein has been used by neuroscientists before in the lab, in order to make 'light switches' that turn neurons of interest on and off in lab animals1. But its use as a therapy against blindness is in very early stages.

If the technique can be perfected, it could allow people rendered totally blind by the loss of photoreceptors able to see — albeit in black and white.

See how they run

Botond Roska of the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland, and his team looked at mice that were entirely missing photoreceptors in their eyes. These photoreceptors usually feed signals about light to the next layer of cells, called bipolar cells, before a signal is relayed on to the brain, providing a visual image.

The researchers used a harmless virus to carry the protein into the mice's bipolar cells. The protein ended up in only about 7% of the cells this way, but that was enough for light signals to be transmitted to the next layer of the retina — the ganglion cells – and eventually the brain, the team determined through studies of brain activity. While untreated mice didn't respond to light at all, treated mice kept in the dark jumped into action when a bright light was turned on, they report in Nature Neuroscience2.

It’s difficult to gauge exactly how well the mice could see after the treatment. The team tested vision, rather than just light perception, by showing the mice a series of moving stripes and seeing if they could follow them. The treated mice were better than untreated animals, but "you can't ask the mouse", says Roska. Mouse vision isn’t that good in the first place, he adds, which makes it harder to tell.

Brain signals

A previous attempt at conferring sight on blind mice by a team based at Wayne State University School of Medicine, Detroit, showed that the same technique could activate the brain’s visual cortex3. But these mice did not change their behaviour when lights were turned on, as the mice in Roska’s study did.

The reason for the difference, Roska suggests, may be that in the previous study, ChR2 was randomly inserted into many cell types in the retina. There are over 60 types of cell here, some of which are switched on by light, and others that are inhibited by it. Slotting the light-sensitive protein into all of these cells means the opposing effects might cancel each other out, says Roska, or muddle up the output to the brain so much that a signal can't be interpreted.

Nonetheless, says Zhuo-Hua Pan, who led the previous study in Detroit, “many of the results of this paper nicely confirmed our early findings”.

Roska and his colleagues are already setting up a collaboration with clinical groups to develop the technique for people. But even then, it’s likely to be a last-chance treatment, says Roska. If even a tiny bit of vision remains, other treatments will likely be more useful for some time, says Roska. "The method should only be used if there’s absolutely no vision left," he says.

References

  1. Boyden, E. S. Nature Neurosci. 8, 1263-1268 (2005).

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  2. Lagali, P. et al. Nature Neurosci. doi:10/1038/nn.2117 (2008).

  3. Bi, A. et al. Neuron 50, 23-33 (2006).

    Article  Google Scholar 

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Smith, K. Blind mice see the light. Nature (2008). https://doi.org/10.1038/news.2008.781

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  • DOI: https://doi.org/10.1038/news.2008.781

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