Gene therapy kickstarts stem cells to help blind mice see

Scientists have partially restored sight in mice with congenital blindness by using gene therapy to activate retinal stem cells.

Humans and mice have supportive cells at the back of the eye called Müller glia cells, which in some animals such as zebrafish act as stem cells - replacing damaged cells to restore sight. However, this is not the case in mammals. Previous studies have shown that Müller glia cells can proliferate in injured mammalian retinas but only a few turned into new retinal cells.

In the current study, researchers have managed to trigger the Müller glia cells into becoming one type of light receptor cell – rod photoreceptors – without needing to injure the animal's eye.

'The biggest takeaway from this paper is that it is possible to reprogramme Müller glia in mammalian retina and partially restore visual function,' said Dr Bo Chen, a lead study author at the Icahn School of Medicine at Mount Sinai in New York City, New York.

Rod photoreceptors help the eye to detect light at lower levels, and also help preserve a second set of photoreceptors in the retina called cones, which are important for colour vision.

The researchers used a two-step process to restore rod photoreceptors in the mice. First, they injected into the retinas of the mice a gene for beta-catenin to encourage the glia cells to divide. Then a second injection containing genes for transcription factors that then encouraged these newly-formed cells to turn into rod photoreceptors, was given.

The study also showed that as well as having a normal appearance, the newly-formed rod photoreceptors behaved similarly to naturally present ones, producing the same characteristic proteins. By using this technique in mice that were born blind the scientists were also able to show that the neurons responded to light and the cells were therefore functional.

To determine how much sight has been regained in these animals, the authors plan on conducting behavioural studies that depend on vision. They also hope to test their technique on human retinal tissue grown in the lab.

'This is an exciting paper, as many labs have been trying to reprogramme Müller glia in mammals for some time now,' Dr Anand Swaroop, a neurobiologist at the National Eye Insititute in Bethesda, Maryland, who was not involved in the study told The Scientist.

While the study may give hope to people with blindness, it is unknown whether the technique will work in humans and clinical trials are a long way off.

Helen Lee at the UK's Royal National Institute of Blind People in London, told The Times: 'Clearly it is still at a very early stage, but at some point in the future stem cell treatment may become part of the armoury of treatments for sight-threatening eye conditions.'

The study was published in Nature.