Nerve cells that normally are not light sensitive in the retinas of blind mice can respond to light when a green algae protein called channelrhodopsin-2 (ChR2) is inserted into the cell membranes, according to a National Institutes of Health (NIH)-supported study published in the April 6, 2006 issue of the journal Neuron. The study was conducted with mice that had been genetically bred to lose rods and cones, the light-sensitive cells in the retina. This condition is similar to the blinding disease retinitis pigmentosa (RP) in humans.
Vision normally begins when rods and cones, also called photoreceptors, respond to light and send signals through the retina and the optic nerve to the visual cortex of the brain, where visual images are formed. Unfortunately, photoreceptors degenerate and die in some genetic diseases, such as RP. Both mice and humans go progressively blind because with the loss of rods and cones there is no signal sent to the brain.
This study, funded by the National Eye Institute (NEI) of the NIH, raises the intriguing possibility that visual function might be restored by conveying light-sensitive properties to other surviving cells in the retina after the rods and cones have died. Principal investigator Zhuo-Hua Pan, Ph.D., of Wayne State University School of Medicine, and his colleagues, using a gene-transfer approach, introduced the light-absorbing protein ChR2 into the mouse retinal cells that survived after the rods and cones had died. These cells became light sensitive and sent signals through the optic nerve to the visual cortex.
"This innovative gene-transfer approach is certainly compelling," said Paul A. Sieving, M.D., Ph.D., director of vision research at the NIH. "This is a clever approach that offers the possibility of some extent of vision restoration at some time in the future." In addition to RP, there are many forms of retinal degenerative eye diseases that possibly could be treated by gene-based therapies.
The researchers determined that the signals reached the visual cortex in a majority of the ChR2-treated mice. The light sensitivity persisted for at least six months. Did the mice regain usable vision? Probably not, but the investigators suggest a number of technical improvements to their experiments which might make that possible.
"This study demonstrates the feasibility of restoring visual responses in mice after they lose the light-sensitive photoreceptor cells," said Dr. Pan. He and his colleague, Alexander Dizhoor, Ph.D., of Pennsylvania College of Optometry, another of the study authors, think that expressing ChR2 in other types of retinal cells may help to improve this approach. In addition, the authors state it would be interesting for further study to modify the light sensitivity and/or wavelength selectivity of ChR2, or use similar microbial proteins, to produce diverse light-sensitive channels to improve outcomes for the possible restoration of normal vision.
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