WSU School of Medicine researchers led by Zhuo-Hua Pan, Ph.D., associate professor of anatomy and cell biology, have reported a new way to restore visual responses in blind mice. This National Eye Institute-supported research is published in today's issue of Neuron.
Vision normally begins when rods and cones, also called photoreceptors, respond to light and send signals to other retinal neurons, called inner retinal neurons (interneurons), and the optic nerve. These signals are transferred to the visual cortex of the brain where visual images are formed.
Unfortunately, in some genetic diseases, such as retinitis pigmentosa, rods and cones degenerate and die, leading to blindness. At present, no treatment is available for restoring vision once rods and cones have been lost.
Dr. Pan and his colleagues took an unprecedented approach to correcting this type of vision loss. Using a harmless virus, they introduced a gene encoded with a light-sensitive protein, called channelrhodopsin-2 (ChR2), from green algae into surviving inner retinal neurons in mice that were genetically bred to lose photoreceptors. They found that the introduced ChR2 protein made the inner retinal neurons become light sensitive. What's more, they found, the ChR2 protein persisted for long periods in these neurons, and the neurons generated signals that were transmitted to the visual cortex of the animals' brains.
"Our study demonstrates the feasibility of restoring visual responses in mice after they lose the light-sensitive photoreceptor cells," said Dr. Pan. "It raises the possibility that this approach may be a potential strategy for the treatment of blindness caused by rod and cone degeneration in humans."
"With this strategy, the investigators have made a paradigm shift in the field and opened the possibility of genetically modifying the surviving retinal interneurons to function as a replacement light-sensing receptor," wrote John Flannery and Kenneth Greenberg of University of California, Berkeley, in a preview of the paper in the same issue of Neuron. "This publication is clearly a significant first step into this new field of re-engineering retinal interneurons as genetically modified 'prosthetic' cells."
Dr. Pan and his colleagues said that further studies are needed to determine whether the light signals reaching the visual cortex can be perceived by the brain as usable vision. Also, they stated, a number of technical improvements will be required to better fit the need for vision restoration.
"This innovative gene-transfer approach is certainly compelling," said Paul A. Sieving, M.D., Ph.D., director of vision research at the National Institutes of Health. "This is a clever approach that offers the possibility of some extent of vision restoration at some time in the future."