Ophthalmology generally, and particularly our centre, is prominent in the field of clinical genetics and the leading causes of blindness such as age-related macular degeneration and retinal dystrophies are more completely understood in terms of the underlying causative genes than in most other systems. A recent step change in genetic sequencing technology occurring over the past ten years has given us the opportunity to leverage this understanding and acquire more genomic and clinical data to improve diagnosis, counselling and clinical care going forwards.
Although single gene causes of blindness are rare, together they affect 5 per cent of the population These eye diseases, however, are a huge burden on the patient, families, carers and society as they cause lifelong, untreatable and permanent blindness. We have recruited extensively to five large studies which will look overall at gene discovery, deep phenotyping, trial recruitment and treatment. These studies as a resource will increase our understanding of the link between gene mutation and eye disease and therefore the counselling and management for patients and families living with these diseases. The studies include NIHR-Bioresource BRIDGE-SPEED study (720 families), the Genomics England Pilot study (220 families), Genomics England (>2100 participants), UK Retinal Disease Consortium (500 families) and the NIHR Translational Research Consortium for Rare Disease (over 700 probands).
We have identified that the majority of genetic risk factors in AMD act early in the disease process. We plan to identify the highest and lowest risk individuals in the population and undertake deep phenotyping to determine structural and functional changes that may occur before patients have started to have symptoms. Diabetic eye disease is a variable and potentially blinding disorder in which unknown genes confer increased susceptibility in some patients. Finding these will increase our understanding of the disorder and improve management. We have the opportunity to collect data from 3000 patients prospectively (ORNATE study – Prof Sivaprasad) to address this important medical challenge.
We are working on using the development of retinal tissue from patient-derived stem cells to provide us with the tools to develop and validate our precision medicine approach for blinding eye diseases. Already, one cause of severe blindness in children has found to be tractable to treatment with specific molecules aimed at the molecular defect (Prof Cheetham) and we intend to expand this approach to understand, and test treatments on such cells from those with other blinding disorders.
- Develop precise diagnosis, novel treatments and improved patient care for single gene causes of blindness
- Define mechanisms, improve treatments and prevent blindness for common multi-factorial blinding conditions
- Implement Precision Medicine through cellular models of specific blinding diseases