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Approved research

Investigating the Genotype-Phenotype Correlations of Rare Complement Factor I Gene Variants in Age-Related Macular Degeneration.

Principal Investigator: Dr Nikolaos Tzoumas
Approved Research ID: 58654
Approval date: June 16th 2020

Lay summary

Age-related macular degeneration (AMD) is the most common cause of severe sight loss in the developed world and an urgent public health issue. Currently, around 600,000 people in the UK have sight loss due to AMD and this is expected to more than double by 2050. AMD is incurable and there are no available treatments for most cases. Although the causes of AMD are not fully understood, genes make a large contribution to disease risk. The best-studied of these genes are involved in a part of the body's immune response known as the complement system, a group of proteins which work together to protect against infections. However, it is unclear how these genetic changes are related to retinal damage and sight loss in AMD. One theory is that mutations affecting the function of these proteins leads to inappropriate complement activation in the eye, leading to damaging inflammation which may cause or worsen AMD. Although therapies to block complement have been very successful in treating rare kidney conditions, most patients with AMD fail to respond. Recently, rare mutations in the gene for complement factor I, a protein which controls complement activation, have been very strongly related to AMD. We would like to determine to what extent these rare genetic mutations contribute to AMD risk in the UK population and the natural history of the disease in people carrying these genes. This will help us to understand the causes of AMD and who may be more likely to benefit from future therapies targeting the complement system. Finally, as not all eye disease starts in the eye, our research will improve our understanding of the links between AMD and other diseases.