Gene Insertion Made Blind Mice See

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Gene Insertion Made Blind Mice See

 A form of gene therapy that makes use of an inactivated virus can potentially be used to restore blind people's vision/ Photo By vchalup via 123RF


People who suffer from retinal degeneration are left with electronic eye implants. Neuroscientists today have found an alternative in the form of gene therapy. However, this is still under research. In about three years, this new therapy can be used in clinical trials.

It was fairly easy. Scientists at the University of California, Berkeley inserted a gene for a green-light receptor in the eyes of blind mice. After a month, the mice were able to navigate obstacles normally. They can see motion and brightness changes as well as fine details on an iPad - enough to distinguish letters.

According to researchers, within three years, the gene therapy that was delivered using an inactivated virus can be tried on humans who lost their vision due to retinal degeneration so that they can have enough vision to move around. Eventually, their vision can be restored and they can read and watch again.

Ehud Isacoff, a UC Berkeley professor of molecular and cell biology and director of the Helen Wills Neuroscience Institute, said that the virus is injected into the eye of the patient and a few months later, they'd be able to see something. With neurodegenerative diseases of the retina, people would usually try to slow down the degeneration. But something that is able to make you see more is an amazing thing, according to Isacoff.

About 170 million people globally are suffering from age-related macular degeneration. This happens to one in 10 people over the age of 55 while 1.7 million people worldwide have the common inherited blindness, and retinitis pigmentosa that leaves people blind by the age of 40.

"I have friends with no light perception, and their lifestyle is heart-wrenching," said John Flannery. He is a UC Berkeley professor of molecular and cell biology who is part of the School of Optometry faculty. "They have to consider what sighted people take for granted. For example, every time they go to a hotel, each room layout is a little different, and they need somebody to walk them around the room while they build a 3D map in their head. Everyday objects, like a low coffee table, can be a falling hazard. The burden of disease is enormous among people with severe, disabling vision loss, and they may be the first candidates for this kind of therapy," he added.

As of today, the option for such patients is only an electronic eye implant hooked to a video camera on top of a pair of glasses. This can be an expensive setup.

Treating humans using gene insertion is more complicated because the human eye has a thousand times more ganglion cells than the eye of a mouse/ Photo By taa22 via 123RF


It is not easy to correct the genetic defect responsible for retinal degeneration. There are more than 250 genetic mutations that are responsible for retinitis pigmentosa. Majority of this -- about 90%, kills the photoreceptor cells on the retina, such as the rods, which are sensitive to dim light, and the cones, for daylight vision. Retinal degeneration does not affect other layers of retinal cells including the bipolar and retinal ganglion cells. These can remain healthy for decades after people have become totally blind, though they are not responsive to light.

Based on the UC Berkeley team's mice trial, they were able to make 90% of the ganglion cells light-sensitive.

How the study was done

To reverse the blindness in mice, researchers have designed a virus that will target retinal ganglion cells. Then they loaded it with a gene for a light-sensitive receptor, the green cone opsin. Opsin is usually expressed by cone photoreceptor cells and makes them sensitive to green-yellow light. When this is injected into the eye, the virus carries the gene to the ganglion cells that are insensitive to light and then makes them sensitive to light. It then sends a signal to the brain that can be interpreted as sight.

"To the limits that we can test the mice, you can't tell the optogenetically-treated mice's behavior from the normal mice without special equipment," Flannery said. "It remains to be seen what that translates to in a patient."

The scientists were able to administer the opsin to the ganglion cells in the retina. However, treating humans is a different thing because more virus particles are required since the human eye contains thousands more ganglion cells than the eye of the mouse. The UC Berkeley has found a means to enhance viral delivery in order to insert new light sensor to a high percentage of ganglion cells.

After more than a decade of trying out different schemes, Isacoff and Flannery finally came up with a simple fix. While other methods they did have worked, they did not achieve the sensitivity of normal vision.

In order to capture the high sensitivity of natural vision, Isacoff and Flannery turned to the light receptor opsins of photoceptor cells. They used adeno-associated virus (AAV) that naturally injects ganglion cells. They then delivered the gene for a retinal opsin into the genome of the ganglion cells. These made the blind mice see for the entire duration of their lives. After a while, humans might also benefit from it.