Gene-based treatments for eye diseases advance in the battle against blindness and related life-threatening conditions
Genetic research into eye diseases is important; heritable eye diseases are a major cause of blindness among children and working-age adults. Genetic insights into more common eye diseases matter too, since they increasingly affect an ageing population; around two million people in the UK today are living with sight loss.
Personalised medicine through genomics
Next generation sequencing panel-based diagnostic testing is available for mutations in almost 200 different genes linked with inherited retinal diseases. This testing is particularly useful in conditions such as cone rod dystropies, where the causal mutation for an individual may be in one of many different genes.
Genome-wide association studies are helping boost understanding of the contribution of common genetic variants to risk of age related macular degeneration (ARMD). For example, a combination of variants in the complement factor H and ARMS2/HTRA1 genes confers up to 40 times increased susceptibility to developing ARMD. This sort of finding can inform the development of potential new treatments, and might one day also contribute to risk prediction and prevention.
Pharmacogenetics can be important in ophthalmology, too. The sight-threatening condition uveitis is typically treated with the immunosuppressant drug azathioprine. Testing for gene mutations in the TPMT gene, which produces the enzyme responsible for metabolising the toxic by-products azathioprine, can identify patients who are enzyme deficient and avoid severe adverse responses to normal medication levels.
Looking beyond the eye
Eye disorders can have implications beyond loss of vision; some are linked to cancers and renal diseases. In patients presenting with a specific eye condition, genetic testing can identify the presence of mutations associated with other life-threatening conditions and aid clinical management:
- Loss of function in the RB1 tumour suppressor gene during retinal development can result in the development Retinoblastoma, which typically presents in children under six
- For uveal melanoma, gene testing can identify patients with a loss of chromosome 3 (monosomy 3) and a mutation that inactivates BAP1, who show increased propensity to metastatic spread
- Genomic analysis of patients with LCA may reveal mutations in genes such as IQCB1 and IFT140 that can be associated with development of the progressive renal disease nephronophthisis
There are clearly some hurdles to leap before gene-based treatments for eye diseases will be widely seen in clinics, but as a tool to improve screening, risk prediction and clinical management, genomic technology is already helping patients.