Degenerative retinal disease is a problem for millions of people worldwide, as light-sensitive cells called photoreceptors at the back of the eye die without being replaced. Thanks to new research, a solution to the problem might not be far off.
Scientists in Canada have come up with a way to transform dormant support neurons called Müller glial cells into tissues that work like cone photoreceptors, which are required for color perception and visual acuity. While the process has only been tested on mice cells, it could eventually be developed into a therapy that can restore vision in people.
Part of the reason the Müller glial cells were chosen for investigation is their ability to be reprogrammed in some animals. Unfortunately it's not a trick that these cells can do in humans.
"What's interesting is that these Müller cells are known to reactivate and regenerate retina in fish," says neuroscientist and first author Camille Boudreau-Pinsonneault from the University of Montreal.
"But in mammals, including humans, they don't normally do so, not after injury or disease. And we don't yet fully understand why."
Key to the study were the genes Ikzf1 and Ikzf4, and the proteins they produced. These proteins are known as temporal identity factors, already known to play important roles in the development of cells into various types.
The Müller glial cells were isolated and cultured before being reprogrammed using a variety of temporal identity factors, including Ikzf1 and Ikzf4. These factors didn't fully transform the glial cells into cone cells, but they did take on some of the necessary characteristics to function like the photoreceptors.
While glial cells help nourish, regulate, and organize other cells in the eye, the researchers say there's enough of a surplus to safely convert a number of the support cells into the photoreceptor-like cells – crucial for seeing light and identifying colors.
It's early days, but the process could eventually be adapted to work in humans, without the need to transplant any new cells. Further down the line, these findings could also be useful in treating diseases in the brain – being able to replace certain neurons that have been damaged by reprogramming other types of cells.
There's a lot more work to do, but this is a very promising start. Next the team wants to look more closely at the mechanisms involved in this cell transformation, and to investigate ways in which it could be made more efficient.
"[W]e may one day be able to take advantage of the cells that are normally present in the retina and stimulate them to regenerate retinal cells lost to pathological conditions and to restore vision," says doctoral student Ajay David from the University of Montreal.
The research has been published in PNAS.