Genotype-phenotype study of CRB1-retinopathy

Brief Lay Background

Inherited retinopathies are a group of eye diseases that affect the retina, the light-sensitive tissue at the back of the eye. They are all caused by at least one gene that is not working properly.

In people with inherited retinopathies, the light-sensing cells (photoreceptors) in the retina stop working and eventually die – causing progressive sight loss, often leading to blindness.

What problem/knowledge gap does it help address

Researchers have identified that faults in the CRB1 gene can cause different inherited retinopathies: Leber congenital amaurosis (LCA) which causes severe sight loss at an early age – and retinitis pigmentosa (RP) and cone-rod dystrophies that tend to start later in childhood or early adulthood. But exactly when an individual’s sight loss will start and how quickly it worsens varies from person to person.  

It is not understood why specific faults in the CRB1 gene can cause different retinopathies with such varied patterns of sight loss – meaning doctors can't predict both the severity and how quickly a person’s sight loss will progress.

Aim of the research project

To improve understanding of the natural history (or progression) of inherited retinopathies caused by faults in the CRB1 gene.

Key procedures/objectives

1. Collect data from 111 patients with CRB1 faults – and use this to examine the time course of the disease and identify any connections between the exact genetic change and specific clinical features.
2. Study groups of patients with LCA, RP and cone-rod dystrophy using state-of-the-art imaging tests over two years to determine appropriate measures that could be used in future clinical trials. 
3. Compare more child-friendly tests with standard investigations to find out if there are similar, more accurate and reliable alternatives for measuring sight changes in children with LCA and RP in the future.
4. Investigate whether faults in the CRB1 genes can have an impact on brain structure and function in RP and LCA patients.

Potential impact on people with sight loss

Novel gene therapies are in development to correct the underlying cause of inherited retinopathies caused by faults in the CRB1 gene. This research could help determine which patients might benefit from these and other innovative treatments in the future. 

It could also help doctors to provide better advice to each patient on the likely progression of their disease – and improve future clinical trials investigating the effectiveness of potential new treatments that could help slow down or stop sight loss.