Blind Mice Regain Sight with a Single Gene Insertion

Scientists from the University of California, Berkeley, inserted a gene for a green-light receptor into the eyes of blind mice. A month later, they could easily navigate around obstacles, see motion and brightness changes over a thousand-fold range, and distinguish letters on an iPad. In time, the virally delivered gene therapy could be tested in humans who have lost sight due to retinal degeneration. The findings were published today in Nature Communications.

“You would inject this virus into a person’s eye and, a couple months later, they’d be seeing something,” says senior author Ehud Isacoff. “With neurodegenerative diseases of the retina, often all people try to do is halt or slow further degeneration. But something that restores an image in a few months—it is an amazing thing to think about.”

About 170 million people worldwide live with age-related macular degeneration, which strikes one in ten people over the age of 55, while 1.7 million people worldwide have the most common form of inherited blindness—retinitis pigmentosa—which typically leaves people blind by the age of 40.

Currently, options for such patients are limited to an electronic eye implant hooked to a video camera that sits on a pair of glasses—an awkward, invasive, and expensive setup that produces an image that is equivalent to a few hundred pixels. Normal, sharp vision involves millions of pixels.

Correcting the genetic defect responsible for retinal degeneration is not straightforward, either, because there are more than 250 different genetic mutations responsible for retinitis pigmentosa alone. About 90% of these kill the retina’s photoreceptor cells. But retinal degeneration typically spares other layers of retinal cells, including the bipolar and the retinal ganglion cells, which can remain healthy, though insensitive to light, for decades after people become totally blind. In their trials in mice, the UC Berkeley team succeeded in making 90% of ganglion cells light sensitive.

“That this system works is really, really satisfying, in part because it's also very simple,” Isacoff says. “Ironically, you could have done this 20 years ago.”

The UC Berkeley team is now at work testing variations on the theme that could restore color vision and further increase acuity and adaptation.

Image: Adeno-associated viruses (AAV) engineered to target specific cells in the retina can be injected directly into the vitreous of the eye to deliver genes more precisely than can be done with wild type AAVs, which have to be injected directly under the retina. UC Berkeley neuroscientists have taken AAVs targeted to ganglion cells, loaded them with a gene for green opsin, and made the normally blind ganglion cells sensitive to light. Image courtesy of John Flannery, UC Berkeley.