See blind mice: algae gene makes sightless eyes sense light.

Scientists have prompted mouse-eye cells that aren't normally light sensitive to respond to light. This strategy could lead to new treatments for retinitis pigmentosa and related diseases, which cause blindness in 1 in 3,000 people worldwide.

These diseases occur when the retina's light-sensing cells die. Called rods and cones, these cells--when healthy--convert light into an electrical signal. That signal then passes to nearby cells and eventually reaches the brain, where it's interpreted as vision. If rods and cones die, they aren't replaced.

To restore vision in people who have lost these cells, scientists have suggested several strategies, such as growing rods and cones from stem cells or replacing them with synthetic chips that sense light. But so far, these approaches face myriad challenges.

The new work took a gamble on some preliminary findings that indicated that other cells in the retina continue to function after the rods and cones die. These spared cells include inner retinal neurons, nerve cells that process information from rods and cones before sending it to the brain.

"We came up with the idea that if we can convert these neurons into light sensors, then that might be a way to restore vision," says Zhuo-Hua Pan, a neuroscientist at Wayne State University School of Medicine in Detroit.

To do this, Pan and his colleagues borrowed a gene from green algae. It codes for a light-sensing protein, called channel-rhodopsin-2 (ChR2), that forms on algal cell surfaces. Algae use this protein to detect light, which they swim toward to maximize photosynthesis.

The researchers inserted the ChR2 gene into a harmless virus and then let the virus infect the eyes of healthy mice. Individual inner retinal neurons that carried the light-sensing algal gene generated an electric current when Pan's team shined light on them.

Next, the researchers worked with mice that were genetically predisposed to lose all their rods and cones by a few months of age. The team infected the eyes of blind adult mice with the viruses carrying the ChR2 gene, and the inner retinal neurons became sensitive to light.

To see whether the electrical signal generated by these cells made it all the way to the brain, Pan and his colleagues inserted electrodes into the brain area that processes sight. When they shined a light on the rodents' eyes, the researchers saw an electrical response. Pan's team reports these results in the April 6 Neuron.

Although the light-generated signals reached the brains, Pan notes that it's not yet possible to say whether the blind animals could then see. The genetic condition that affects the mice kills the majority of the rods and cones before a newborn opens its eyes. Because vision is shaped by experience, Pan says, the rodents' brains may not interpret these signals as sight. He and his team plan on developing tests for sight in other animal models for future experiments.

Nonetheless, these preliminary findings offer a novel approach to treat blinding diseases, neuroscientists John G. Flannery and Kenneth P. Greenberg of the University of California, Berkeley note in a commentary accompanying the new report. The study is "clearly a significant first step into this new field of re-engineering [inner retinal neurons] as genetically modified 'prosthetic' cells," they say.