Reversing blindness is a challenge for science. This question has been investigated for years from different angles. A group of American scientists published very promising results a few months ago after treating patients with hereditary retinal degeneration with an experimental “gene editing” therapy. Most improved their vision after changing a genetic mutation.
Today, researcher Pia Cosma, from the Center for Genomic Regulation (CRG) in Barcelona, wants to open a new avenue of exploration. He proposed creating a synthetic retina from stem cells that he will first test in mice. If it works, the idea is to translate it to humans with retinitis pigmentosa, a rare, degenerative disease that gradually leads to vision loss. The project, financed by the La Caixa Foundation to the tune of almost one million euros, will be carried out in collaboration with biotechnologists from Do Minho University (Portugal).
For those who have just landed on this pathology: what is retinitis pigmentosa and what does it cause in patients?
It is a rare degenerative pathology – it affects one in 3,000 to 5,000 people – and patients gradually lose their retinal photoreceptors. These are cells that convert light into electrical signals transmitted to the brain. In other words, it allows images to be created in the brain. The retina is like a small brain that has different layers of neurons, different layers.
Is there currently a treatment to prevent this degeneration?
There are options to slow or progress degeneration, but not to stop it. The speed depends on the mutation, but there is a moment when we cannot see it. Our research is designed for late-stage patients, if it actually goes as we hope. The only thing currently being tested is gene therapy for specific mutations, i.e. solutions for certain patients. But only for some.
This is where the heart of their project comes in: creating a synthetic retina. How is this done in the laboratory?
We will create a specific type of retina which is a kind of organoid integrated into a biostructure capable of creating an optic nerve. How ? Through the reprogramming of pluripotent stem cells, we create a tissue similar to the retina inserted in a kind of scaffolding that encapsulates it and promotes the formation of an organoid suitable for transplantation. In other words, it connects to what still works.
So the retina doesn’t completely die?
No, the retina does not lose all its functions with this disease because it has different layers of neurons. The most affected are the photoreceptors but they synapse with interneurons and ganglion cells. When there is severe degeneration, other neurons are somewhat damaged. However, they still work somehow.
Should they test it on mice first?
Yes, when we succeed, we will transplant it into mouse models in this degenerated part, but which still maintains the connection with the brain. There we will see how it works and if the problem is solved. We will also use mouse and human stem cells.
If it works, will it work for more pathologies or just for this one?
This project could resolve other types of pathologies involving photoreceptor degeneration. And what’s more, since we will be creating an organoid with an optic nerve, we could study pathologies linked to lesions in this area, such as glaucoma. For the moment we have chosen retinitis pigmentosa because we know it well. I hope we succeed.
