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

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.

Regenerative therapies, by contrast, 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 groups 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, like 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, 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 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 at University College London 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.

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.

This project has been disrupted by laboratory closures during COVID-19 lockdown measures and it will require further time and funding to reach its successful completion. Please give today, if you can.