UC Berkeley Researchers Restore Vision in Blind Mice with Single Gene Injection

By inserting a single gene for a green light receptor into the eyes of blind mice, scientists from the University of California, Berkeley, were able to restore their vision. These effects were observed one month after genetic alteration, with the mice navigating around obstacles as easily as the mice with no history of visual defects. They were also able to detect motion, brightness changes and fine detail on a screen to distinguish letters.

To correct the blindness in these mice, the researchers created a virus that targeted retinal ganglion cells and equipped it with the gene for the green cone opsin, a light-sensitive receptor. This opsin is normally expressed by cone photoreceptor cells that allow them to detect green-yellow light. Injecting this into the eye allowed the virus to encode this gene into the ganglion cells that normally are not light sensitive. Doing so transformed these cells to be light-sensitive and enabled them to send signals to the brain that were interpreted as vision.

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The utility of this injection method is that it can be done easily through the eye. The earlier versions of such viral therapy required the injecting of viruses underneath the retina. This means of gene therapy uniquely transforms non-visual cells in the retina to takeover the light-sensing function of the rods and cones.

The researchers claim that in as little as three years, the gene therapy could be used in trials in humans who have lost vision due to retinal degeneration. Ideally, this would give these patients enough vision to move around and potentially be able to read or watch video.

“You would inject this virus into a person’s eye and, a couple months later, they’d be seeing something,” said Ehud Isacoff, UC Berkeley professor of molecular and cell biology and director of the Helen Wills Neuroscience Institute. “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.”

With roughly 170 million people living with age-related macular degeneration and 1.7 million having retinitis pigmentosa, the most common form of heritable blindness, gene therapy that could restore vision in patients would have a profound impact in this community.

The existing treatment option for these patients is currently an electronic eye implant that is connected to a video camera on a pair of glasses. This tool produces an image on the retina that is roughly a few hundred pixels, whereas millions of pixels are required for sharp vision. In addition to yielding low quality images, these glasses are bulky, invasive, and expensive as well.

In the mice, the researchers were able to administer the opsins to most of the retinal ganglion cells, but in humans they will need to inject many more of the virus since the human eye has many more of these ganglion cells. The UC Berkeley team has developed methods to enhance viral delivery and hopes to insert the gene in a high percentage of ganglion cells that will compare to the high pixel numbers in a camera.

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Alongside fellow UC Berkeley professor John Flannery, Isacoff is raising funds to apply this gene therapy in human trials in the next three years. Similar adeno-associated virus delivery systems have been approved by the FDA in treating visual defects, and the team hopes to add their gene therapy to this list.

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

Sources: UC Berkeley