Project Grants

Retina UK aims not only to progress research along established threads, but to stimulate new thinking, encourage innovative approaches and nurture original ideas. Our Project Grants support projects of varying length which seek to explore new ideas or test new theories.We have made a commitment to support the talented research teams who are delivering the ground-breaking projects listed below. We are extremely grateful for each and every donation we receive.

Person in white lab coat using a pipette

A major form of RP is caused by defects in components of the “spliceosome”, an important and complex structure within cells. The spliceosome edits unwanted or nonsensical passages out of a set of genetic instructions so that only intelligible code remains for the cell to use. One of the most common causes of RP is a fault in a group of genes that regulate this process.

Thanks to earlier funding from Retina UK, Prof Lako and her team have used stem cell technology to generate retinal cells from patients with mutations in a key gene involved in the splicing process (PRPF31), and have demonstrated that retinal pigmented epithelial (RPE) cells and photoreceptors are affected at the structural and functional level.

The newly funded project aims to develop a PRPF31 gene therapy to increase levels of healthy PRPF31, and use the retinal cell model to assess the therapy’s efficacy in restoring RPE and photoreceptor function. This highly collaborative study, involving four institutions across the UK and Germany, provides a unique opportunity for rapid proof-of-concept, leading to the potential for rapid translation into a Phase I/II clinical trial for PRPF31 RP patients as an immediate outcome. Between them, faulty spliceosome genes are a relatively major cause of RP, so the outcomes of this project should also be applicable to the development of treatments for a wider proportion of our community.

We are now supporting a PhD studentship at Oxford University, co-funded by the Macular Society, that will look into a potential new method for treating Stargardt disease and other conditions where “conventional” gene therapy may not be possible. Under the supervision of Prof Robert MacLaren, the student will investigate whether it is possible to use harmless viruses to carry special molecular tools into retinal cells in order to edit and correct the defective genetic code. Rather than targeting DNA, this technique will aim to edit a different molecule called RNA that copies and then carries the genetic instructions from the centre of the cell to the protein building machinery; the original DNA is hence left unaltered and safety may be improved.

A PhD student supervised by Dr Rob W J Collin at Radboud University in The Netherlands will be studying the different genetic mutations which lead to Stargardt disease – a macular dystrophy which affects people from childhood and for which there is no cure.
Stargardt is usually caused by mutations in the ABCA4 gene. Patients with two severe variants of ABCA4 develop sight loss early, as their code only contains the instructions to make harmful versions of the protein. Other people with a combination of severe and mild mutations produce a mixture of harmful and normal proteins and so tend to avoid symptoms until later.
In some people with later-onset Stargardt, bits of the genetic code are mistakenly “skipped”. So like a recipe with steps missing, the resulting protein doesn’t turn out like it is supposed to.
This project aims to understand how and why bits of the gene are “skipped”, and prevent the misreading of the gene that causes damaging protein versions to be produced. The studentship will enable a promising young scientist to lay the foundations for a future career in inherited sight loss research.

LCA is the most severe form of early-onset retinal degeneration. This projects aims to increase knowledge of the molecular basis of this disease and accelerate development of an effective treatment. Dr Moosajee will develop new disease models, one using stem cells derived from a patient with LCA and one in zebrafish, so that both can be used to increase understanding of the effects of the disease-causing mutation in the RDH12 gene and test the potential of new drug and gene editing treatments.

RP is commonly caused by a fault in a group of genes that regulate the editing of unwanted passages out of a set of genetic instructions, a process known as splicing. Already, the team’s work suggests that retinal cells are much more affected by mis-splicing than other types of cell. The team will continue investigating why this goes wrong in RP, and test new gene therapy treatments in a cell model.

Read the final project report

This project explores an alternative to traditional gene therapy, which may have implications for a wide range of inherited retinal dystrophies, not just Usher syndrome. S/MAR vectors have the capacity to hold much larger genes, and they have no viral components. The team will explore whether this new approach represents a safe and effective future treatment option.