Regenerative therapies to treat retinal dystrophies

Why is this research needed?

Retinal dystrophies are a leading cause of untreatable blindness in the developed world. They are characterised by photoreceptor degeneration and include conditions such as retinitis pigmentosa, macular degeneration, and diabetic retinopathy.  

Photoreceptors are light-sensing neurons located in the retina, at the back of your eye. These are highly specialised cells that are prone to damage and which, once lost, cannot be replaced. Currently, there are few effective therapies and the majority attempt to slow down vision loss.

What is the aim of the project?

Regenerative therapies, aim to reverse vision loss by replacing the dying cells. This field has made significant progress with the development of transplantation of stem cell-derived photoreceptors, with several studies already moving towards clinical trials. However, at present, the process of producing stem cell-derived retinal cells in vitro is costly and time-consuming.

An attractive, but unproven, alternative is to try to unlock the potential for making the retina repair itself. Although the human retina, as in most mammals, is very bad at repairing itself, this is not the case for lower vertebrate species, like fish and frogs. These species have a remarkable capacity for repair after damage. Studies of fish and frogs have revealed key signalling pathways involved in the retinal repair mechanisms. One involves a type of support cell in the retina, called the Müller glia, which retain stem cell-like properties that allow them to re-enter the cell cycle after injury and produce new neurons (nerve cells), including photoreceptors. Importantly, it is even possible to reactivate some of these pathways in the mammalian retina but, so far, regeneration has been fairly limited.

To date, almost all of these studies have been in healthy retinas or in experimental models of disease and injury, rather than of progressive photoreceptor loss, as occurs in many forms of inherited retinal degeneration. However, Müller glia behave very differently in response to acute injury and progressive degeneration.

Professor Rachael Pearson and her team are seeking to target one of the key regenerative signalling pathways and reintroduce it into Müller glia in the diseased mammalian retina. They have made genetic tools to manipulate the expression of specific genes (the set of instructions used to make a particular protein), which they predict will push Müller glia back into the cell cycle and attempt to generate new neurons.

How will this research help to beat sight loss faster?

Based on their preliminary findings, they will test the hypothesis that Müller glia in retinas undergoing progressive photoreceptor loss have the capacity for sustained regenerative responses and that this might be used to treat retinal degenerations in humans, therefore preventing blindness due to photoreceptor degeneration.

Further information

Retinitis pigmentosa is the most common inherited retinal dystrophy. You can find more about its causes and symptoms here.