Retina cells successfully regenerated in mice

Scientists have successfully regenerated cells in the retina of adult mice, an advance that paves the way for novel therapies to reverse vision loss in humans.
Many tissues of our bodies, such as our skin, can heal because they contain stem cells that can divide and differentiate into the type of cells needed to repair damaged tissue. The cells of our retinas, however, lack this ability to regenerate.
As a result, injury to the retina often leads to permanent vision loss.
According to researchers at the University of Washington in the US, zebrafish have a remarkable ability to regenerate damaged tissue, including neural tissue like the retina.

This is possible because the zebrafish retina contains cells called Muller glia that harbour a gene that allows them to regenerate. When these cells sense that the retina has been injured, they turn on this gene, called Ascl1.
The gene codes for a type of protein called a transcription factor. It can affect the activity of many other genes and, therefore, have a major effect on cell function.

In the case of the zebrafish, activation of Ascl1 essentially reprogrammes the glia into stem cells that can change to become all the cell types needed to repair the retina and restore sight.

The scientists created a mouse that had a version of the Ascl1 gene in its Muller glia. The gene was then turned on with an injection of the drug tamoxifen.
Earlier studies by the team had shown that when they activated the gene, the Muller glia would differentiated into retinal cells known as interneurons after an injury to the retina of these mice. These cells play a vital role in sight.
They receive and process signals from the retina's light-detecting cells, the rods and the cones, and transmit them to another set of cells that, in turn, transfer the information to the brain.

In their earlier research, however, the researchers found that activating the gene worked only during the first two weeks after birth.
Eventually they found that genes critical to the Muller glia regeneration were being blocked by molecules that bind to chromosomes.
By using a drug that blocks epigenetic regulation called a histone deacetylase inhibitor, activation of Ascl1 allows the Muller glia in adult mice to differentiate into functioning interneurons.
The researchers demonstrated that these new interneurons integrate into the existing retina, establish connections with other retinal cells, and react normally to signals from the light-detecting retinal cells.
The team hopes to find out if there are other factors that can be activated to allow the Muller glia to regenerate into all the different cell types of the retina.

If so, it might be possible to develop treatments that can repair retinal damage, which is responsible for several common causes of vision loss, they said.
The findings appear in the journal Nature.