Genetic eye disease contributes to over 30% of blindness in children worldwide, and inherited retinal disorders are the leading cause of blindness amongst our working age adults in the UK. Overall only 25% of patients will receive a genetic diagnosis and there are very few therapeutic options available.
Our group is committed to advancing our knowledge of the pathophysiology of genetic eye disease by exploring the molecular and cellular basis of disease using multi-omic approaches in model systems such as zebrafish and human induced pluripotent stem cell derived eye cups. This interrogation has provided insights into intracellular changes including mitochondrial dysfunction, increased phagosomal activity and autophagy in diseased tissue. Knowledge of common disease pathways can aid our development of therapeutics.
Gene therapy has shown significant success for treating inherited retinal diseases. But only genes of a limited size can be accommodated by conventional adeno-associated viral vectors. We are developing non-viral DNA plasmid vectors, which have no upper size limit, to facilitate their delivery to the retina using nanotechnology and the target cell's own transport channels. In addition, we are interested in exploring retina-specific immune sensing of foreign DNA, to maximise the longevity and safety outcomes of these new adaptations of gene therapy.