Scientists bestow sight on blind mice

A protein derived from algae restores light sensitivity in mice lacking photoreceptors, Nature News reported. Scientists hope that this technique can one day be used to treat blindness in humans.

In the human eye, light is detected by photoreceptors, known as rods and cones, which work together with several other types of neurons in the retina to create vision.  In many common forms of blindness, photoreceptors deteriorate with age.  Currently, there is no cure for this type of blindness, but proposed treatments have included electrical stimulation or cell transplantation.

New research suggests that channelrhodopsin-2 (ChR2), a light-activated cation channel, may be an effective and less invasive technique. ChR2 is derived from green algae, where it signals the presence of light for photosynthesis. When activated by light, ChR2 opens and positive ions flow into the cell, causing it to fire signals, according to research at Stanford University.

ChR2 was used in a previous attempt to restore vision in blind mice by a team of researchers led by Zhuo-Hua Pan at Wayne State University School of Medicine, Detroit, in 2006. They introduced the gene for ChR2 into retinal neurons using a harmless virus vector. Although individual neurons responded to light, the animals did not show a behavioral reaction.

The problem lay in the fact that there are many types of neurons in the retina. Some fire signals in response to light, while some respond to darkness. By blindly expressing ChR2 throughout the retina, visual information may be scrambled by the time it reaches the brain, according to Pan and his coauthors.

Instead, ChR2 can be targeted to a specific subclass of neurons, rescuing light sensitivity in blind mice, according to research by Botond Roska of the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland (published online in Nature Neuroscience on Apr 27 2008). Roska’s team targeted specific neurons in the retina, known as ON bipolar cells, which normally respond to increases in light. This approach therefore utilized more of the natural circuitry in the degenerate retina.

In addition to confirming the previous results from Pan’s lab in Detroit, Roska’s mice showed increased movement in response to light, and also demonstrated improved visual tracking of a moving image. Therefore, information was successfully sent from the degenerate eyes to the brain.

According to the authors, their results “suggest that ChR2-based stimulation techniques have the potential to restore vision in humans with retinal degeneration.”

Zhuo-Hua Pan, who led the previous research, said in an interview that “further experiments that clearly demonstrate the restored visual perception will be required to address the question” of how functional the restored vision actually is. 

Further limitations include the fact that “some recent studies reported bipolar cells … are severely corrupted after photoreceptor degeneration,” Pan said. Therefore, in many forms of blindness, the visual circuitry may be too degraded for this treatment to work. 

Also, the technique used to target ON bipolar cells, electroporation, probably cannot be used in humans, since it uses direct electrical currents to force DNA into cells.

“It should be noted that since electroporation is unlikely to be a viable treatment approach for patients, it will still be a big challenge to achieve the targeted expression to ON bipolar cells by using virus vectors,” Pan said.

We will have to wait and see whether algae proteins will ever be used to treat human blindness.

Further reading:

Bi, A. et al. “Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration.” Neuron 2006. Vol. 50. pp. 23 – 33.

Boyden, E. S. “Millesecond-timescale, genetically targeted optical control of neural activity.” Nature Neurosci. 2005. Vol. 8. pp. 1263 – 1268.

Lagali, P. et al. “Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration.” Nature Neurosci. 27 April 2008. doi:10/1038/nn.2117.

Smith, Kerri. “Blind mice see the light.” Nature News. 25 April 2008. http://www.nature.com/news/2008/080425/full/news.2008.781.html

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One Comment

  1. Your article is well written and very informative. I have sent a copy to a friend who is interested in the topic of sight. He is an authority on macular degeneration and retinal problems. It is great to have this publication on a website! WS

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