The leukocyte RNA imprint of splicing-factor retinitis pigmentosa

Study code

Lead researcher
Andrew Webster

Study type
Participant re-contact

Institution or company
Moorfields Eye Hospital

Researcher type

Speciality area
Genomics and Rare Diseases


Retinal dystrophies are problems occurring in the retina, the light sensitive layer of the eye, causing progressive visual loss in affected persons. Treatments are limited, but knowledge of their underlying molecular and cellular pathology is leading to gene-directed treatments and prevention of blindness in some.

A significant proportion of these disorders is due to mutations in genes that affect a very ancient and ubiquitous pathway known as gene-splicing. In all living things, excepting bacteria, genes within our DNA need to be converted by this process before they can be translated into proteins, the molecules that make a direct impact on living processes. Peculiarly, when a subset of the genes controlling ‘splicing’ are partially disabled, the most susceptible cell is the rod photoreceptor of the retina. These cells gradually die away and lead to complete loss of the peripheral and later central visual fields.

The reason why the rod photoreceptor is specifically susceptible is unknown. One hypothesis is that these splicing factors have a second ‘moonlighting’ function in these cells. An opposing one is that splicing is more important in these cells than others. If the latter, the splicing defect should be detectable in all cells including those most accessible – the blood white cells.

This project aims to determine which is true, to detect (or not) an ‘endophenotype’ in blood for these disorders, and to understand the downstream biological pathways that are most affected. The patients were recalled from the Inherited Retinal Dystrophy (IRD) cohort at the Rare Diseases BioResource.

This study is part of our Rare Diseases RNA Phenotyping Project. Each participating study in the project is included in a collection hosted on our main studies page.