Blind might one day see, suggest new studies in humans and mice: genetic tricks offer a light at the end of the tunnel.

SEEING THE LIGHT MIGHT NOW GET easier for people with a rare, genetic form of blindness. And studies on blind mice offer hope that people who have lost all the light processing cells in their eyes might not have to stay in the dark.

Gene therapy restored sight in three people with an inherited form of blindness called Leber's congenital amaurosis, researchers reported online April 27 in the New England Journal of Medicine.

The blinding disease results from mutations in the gene RPE65, which encodes a protein that helps rod cells in the eye recycle light-gathering pigments. Cone cells can take over for a while but also start to break down, usually resulting in blindness before age 40. About 2,000 to 3,000 people in the United States have the disease.

Researchers at the University of Pennsylvania and their colleagues injected the right eyes of three people who have the degenerative eye disease with an engineered virus containing a healthy copy of RPE65. All three people had improved vision a few weeks later in their right eyes. Two of the people were only able to distinguish hand movements before surgery. After treatment, the patients could read up to three lines on an eye chart.

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Eye charts are subjective measures of sight, says Katherine High, director of the Center for Cellular and Molecular Therapeutics at Children's Hospital of Philadelphia, which sponsored the study. But the patients also improved on objective tests. When light was shone in patients' treated eyes, their pupils contracted, indicating that their retinas detected light.

"There's no teaching of that," High says. "It's just a reflex."

None of the patients regained 20/20 vision, says Jean Bennett, a molecular geneticist at the University of Pennsylvania who led the team. But all of them report better vision in dim light and increased ability to navigate.

"The improvement that we might think is trivial makes a big difference for them in terms of the quality of their lives," Bennett says.

Using a different method, another team restored vision in mice whose retinas had lost all the light-detecting rod and cone cells--without which mice and other animals, including humans, can't see. The results were published online April 27 in Nature Neuroscience.

Once these photoreceptor cells die, as happens in diseases such as retinitis pigmentosa or macular degeneration, there are few options for restoring them. Some researchers have tried stimulating retinas with electricity.

In 2006, scientists at Wayne State University in Detroit reported that they had inserted a gene for a light-gathering protein from a green algae, Chlamydomonas reinhardtii, into the retinas of mice with a disease similar to retinitis pigmentosa. The protein enabled the mice's damaged eyes to send messages to the brain when stimulated by light, but whether the algal protein or electrical stimulation of the entire retina could actually restore vision was unclear.

Now, Botond Roska, a neuroscientist at the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland, and his colleagues have inserted the light-gathering algal protein (ChR2) into certain cells in the retina's second layer. The secondary cells are called ON bipolar cells because they respond to brightening light, as when lights are turned on. Counterpart cells called OFF bipolar cells react to dimming light.

ON and OFF cells normally pass signals from rods and cones to the brain's visual center, so directly stimulating the cells should restore vision. Roska and his team showed that's just what happens.

The team used electrical current to infuse a piece of DNA carrying the gene ChR2 into ON bipolar cells. The gene is controlled by a piece of DNA that allows it to turn on only in those cells. The technique produces protein only temporarily, so a more permanent method is needed to treat humans.

Blind mice engineered to make the protein ChR2 in their ON cells scurry for cover when exposed to bright light just as normal mice do. Blind mice without the treatment don't respond to the light.

And the protein is "not just acting as a light sensor, it is activating visual systems in the brain," Roska says. A second test indicated that the vision-restored mice could make out lines on a rotating drum about half as well as mice with normal sight.

Algal proteins have a long a way to go before they make it into human eyes, experts agree. Researchers must first design viruses or other delivery mechanisms that can steer the light-gathering molecule only to ON cells. Still, the technique will not restore normal sight, Roska warns--just perhaps the ability to see objects (but not colors).

The algal protein is less sensitive to light and doesn't respond as well to changing light as rods and cones, so people would also need to wear devices that can even out lighting, Roska says. But "any improvement for patients is dramatic."