Modelling and rescue of inherited retinal diseases using induced pluripotent stem cell (iPSC)-derived retinal cells and organoids

Research summary

The retina is the light-sensitive nerve layer that lines the inside of the back of the eye and converts light into electrical signals that is transmitted to the brain via the optic nerve. Inherited retinal diseases (IRDs) are characterised by retinal degeneration associated with genetic mutations. IRDs can affect individuals at any age and progress at different rates with worsening sight or blindness over time. The blinding nature of IRDs, lack of treatment, and complex heterogeneity associated to these conditions highlight the need for research and therapeutic innovation. Retinal gene therapy has great potential for the treatment of IRDs as demonstrated by recent FDA and NICE approval of Luxturna for Leber congenital amaurosis as well as encouraging results from clinical trials in choroideremia and X-linked retinitis pigmentosa. Two main challenges in developing effective therapies for IRDs relate to the absence of suitable experimental models that recapitulate the human clinical phenotype, and the lack of understanding of pathogenic mechanisms underlying retinal degeneration which may be unique to primates. In this study we plan to generate retinal cells and organoids from peripheral blood samples taken from patients with diagnosed IRDs. This would require first turning the blood cells into induced pluripotent stem cells (iPSCs) using established laboratory techniques. The iPSCs could be maintained in culture and differentiated into retinal cell types or retinal organoids. We will use the retinal organoids/cells as a model to study anatomical, functional and molecular characteristics of retinal organoid cultures with a view to assessing potential clinical treatments in a research setting. This might include, for instance, gene therapy, cell therapy, immunology, transplantation and/or gene editing technologies.

Principal Investigator

Prof Robert MacLaren

Contact us

Email: ERGO@ouh.nhs.uk

IRAS number

301603