Seeking solutions to retinal degeneration in inherited retinal diseases

Why is this research needed?

Inherited retinal diseases (IRD) are the commonest cause of blindness amongst working age adults in the UK, and the second most common cause in children. They are caused by mutations in our genetic code and there is currently no cure or specific treatment available.

IRD affect the retina, the light-sensing layer at the back of the eye that converts light into chemical signals that pass to the brain to help us to see. The retina is made up of light-sensing cells called photoreceptors. The death of these cells, and subsequent visual impairment, is a key feature of most inherited retinal diseases.

Researchers have identified some 250 genes that, if mutated, can cause IRD. Developing a therapy to correct each one of these faulty genes would be extremely challenging, time-consuming, and costly. However, there could be another solution that focuses on a single, fundamental aspect of retinal degeneration: the death of photoreceptors.

Recent advances in the understanding of the mechanisms of photoreceptor death have emphasised a particular aspect of the process that could hold the key to preventing these light-sensing cells from dying. Research findings have shown that cellular death in photoreceptors is linked to a failure in energy production (metabolism), and in particular, a failure of sugar (glucose) being used by photoreceptors to produce energy.

What is the aim of the project?

Dr Mariya Moosajee is leading a research project with her team at UCL to test the idea that enhancing photoreceptor energy production can prevent or slow cell death, and therefore lead to the development of a universal treatment for IRDs, regardless of their genetic basis.

Using a disease model that replicates the retinal degeneration caused by two specific genetic mutations, the team will attempt to manipulate the amount of glucose uptake in the retina by increasing the number of glucose transporters and energy-producing metabolic enzymes within specific cells in the retina.

The team will assess the impact of these interventions on photoreceptor metabolism by monitoring the amount of energy molecules produced, the amount of oxygen used, and patterns of gene function. Photoreceptor cell survival will be assessed by investigating the structure of the treated retina, measuring levels of cell death, and testing the resulting vision.

How will this research help to beat sight loss faster?

If the project’s hypothesis is proved correct, Dr Moosajee’s team will be able to further develop their research through additional funding or partnership with industry, to create a gene therapy designed to enhance glucose uptake or metabolism within the retina.

Over 100,000 people in the UK, many of them children, have an inherited eye condition that affects their retina or cornea. The development of a treatment that could prevent, halt, or slow the degeneration of the retina by enhancing energy production within its cells, would be of huge benefit to people living with currently incurable blinding disease.

Further information

The most common type of IRD is retinitis pigmentosa. You can find out more about this disease here.