Corneal disorders comprise the second leading cause of blindness worldwide. One important cause of vision loss is a group of approximately 20 eye diseases known as corneal dystrophy – inherited disorders of the cornea.
The hallmark of corneal dystrophy is structural abnormality of the cornea, including cell fragility and/or accumulation of proteinaceous aggregates, and/or corneal scarring, all of which lead to loss of transparency, visual impairment and ultimately corneal blindness. Pathology can be limited to the outer layer of epithelial cells of the eye as is the case in Meesmann epithelial corneal dystrophy (MECD), or it can also be evident deeper in the eye within the stromal layer as seen in lattice and granular dystrophies. Devastating in itself, corneal dystrophy adds further stress to affected parents as they will pass it on to half their children.
We use preclinical models to investigate the potential of gene therapy for corneal dystrophies. Mutations which cause corneal dystrophy do so by dominant-negative interference therefore conventional gene replacement therapy is not suitable as the dominating mutant would impede the replacement gene.
The team are currently investigating promising therapeutic agents to potently and specifically silence mutant alleles (RNA interference – RNAi), allowing the wild type allele to function normally, and agents which can knock down and replace the mutant gene (snoMEN system). We believe that this proof of principle for gene silencing therapy, will greatly inform gene therapy in the general field of personalised and regenerative medicine. Our approach combines state-of-the-art surgical, molecular genetic and stem cell therapeutic approaches, which is possible due to the eclectic mix of clinical and scientific team members.
Research interests focus on the disorders of the ocular surface, the associated genetics and the immunological responses involved. Core scientific research investigates the ocular surface using cells and donor tissue in preclinical models to assess therapeutic approaches in translational patient based research.
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