Reprogramming retina cells found to reverse blindness in mice
In future, the Three Blind Mice might be able to avoid running into the farmer's wife, if new research out of the National Eye Institute (NEI) pans out. In the study, scientists managed to restore vision in mice born with congenital blindness, using gene therapy to reprogram base retinal cells into functioning rod photoreceptors.
We owe our vision to an array of photoreceptor cells on our retinas, which respond to light and send the signals to the brain to interpret what we're seeing. But being neurons these cells won't regenerate on their own, so if they're damaged, that's it. At least, that's how it works in mammals – scientists have found that other animals like the zebrafish can convert structural cells called Müller glia into new, functioning photoreceptors to restore their vision. The new study has now shown how this could be done in mammals.
"This is the first report of scientists reprogramming Müller glia to become functional rod photoreceptors in the mammalian retina," says Thomas N. Greenwell, NEI program director for retinal neuroscience. "Rods allow us to see in low light, but they may also help preserve cone photoreceptors, which are important for color vision and high visual acuity. Cones tend to die in later-stage eye diseases. If rods can be regenerated from inside the eye, this might be a strategy for treating diseases of the eye that affect photoreceptors."
The team investigated whether this kind of repair mechanism could be carried over to mammals, ideally without having to injure the retinas of test mice. Eventually they developed a two-phase process that managed to do just that. In the first phase, the researchers injected the eyes of healthy mice with a gene that would turn on a protein called beta-catenin. This triggers the Müller glia to start dividing. After a few weeks, phase two involved injecting factors into the eyes that direct those newly-divided cells to develop into rods.
When the team examined the cells using microscopy, they found that structurally the rods grown out of Müller glia looked exactly the same as the natural ones. On top of that, they also developed the network of synapses that allowed them to communicate with other neurons.
In the next test, the researchers tried the treatment in mice born with congenital blindness, meaning they had no functional rods to begin with. Sure enough, rods grown out of Müller glia developed normally, and functionally they were found to communicate with other neurons, even successfully integrating into the visual pathway circuitry.
The next steps for the team are to test how well the mice now perform at visual tasks, and test whether the treatment works on human retina cells in a lab culture.
The research was published in the journal Nature.
Source: National Eye Institute