Understanding a molecular mechanism as a cause of retinitis pigmentosa

Brief Lay background

Retinitis pigmentosa (RP) describes a group of closely related inherited eye conditions that affect the retina – the specialised light-sensitive tissue at the back of the eye.

RP is the most common inherited eye condition, affecting around one in 4,000 people in the UK.

A person’s sight loss usually happens gradually, over many years – and sometimes eventually leads to registered blindness.

What problem/knowledge gap does it help address

The retina contains millions of light-sensing cells (photoreceptors), which are vital for healthy eyesight. In patients with retinal degenerative disorders like RP, the photoreceptors stop working or die – leading to progressive sight loss. Unfortunately, there is currently no known cure or effective treatment that can stop the progression of RP.

Scientists have so far identified faults in more than 60 different genes that can cause RP. Each of these genes contains the instructions for making proteins that are important for maintaining the correct structure and function of photoreceptors.

Scientists are aiming to develop cutting-edge gene therapies that aim to correct the underlying cause of RP in the patient’s photoreceptor cells. But unfortunately, for around four out of ten people with an inherited retinal disorder, it is not currently possible to identify a precise genetic cause – hindering the development of novel targeted treatments for these patients.

Aim of the project

The team has recently identified the genetic cause of RP in many of these unsolved families. But they do not understand how these new and unusual types of genetic fault – which are located in a ‘non-coding’ region of the genome rather than within a gene – interfere with the normal function of the retina.

In this project, they aim to:

1. Uncover a new molecular mechanism behind the development of RP.
2. Investigate the potential of targeted therapeutic approaches to correct the underlying cause of the disease in these patients.

Key procedures/objectives

1. Generate 3D ‘mini retinas’ using stem cells from patients with RP caused by these newly identified genetic faults.
2. Investigate any changes in gene activity and its consequences in these ‘mini retinas’.
3. Explore a variety of experimental approaches – including gene editing – that could help to restore normal gene activity.

Potential impact on people with sight loss

This research could help to improve understanding of the causes of RP – and could one day lead to new targeted treatments that can slow down or reverse sight loss in patients. If successful, this would dramatically improve the quality of life for people with the condition.