Elevated Levels of Complement Factor H-Related Proteins is Associated with Increased Risk of AMD

Article: Breakthrough into leading cause of blindness
Source: Queen Mary University of London (U.K.)
Published: July 13, 2021
Article: Breakthrough into leading cause of blindness
Source: University of Manchester (U.K.)
Published: July 14, 2021

Researchers in the U.K. and Germany conducted a genome-wide association study to investigate genetic variants that determine increased risk of AMD. From 604 blood plasma samples, they identified five proteins, Complement Factor H-Related 1 to 5 (CFHR-1 to CFHR-5), as being higher in individuals with age-related macular degeneration (AMD) than those without the disease. These FHR proteins are part of the complement pathway of the innate immune system. In AMD, the complement pathway is over-activated in the back of the eye, specifically in the intercapillary septa of the retinal pigment epithelium/Bruch's membrane/choriocapillaris (RPE/BrM/CC) complex, leading to a damaging inflammatory response. The findings are novel in the sense that they expand upon earlier information pointing to only Complement Factor H and its protein FH as being implicated in AMD pathogenesis. The study also employed technological advances in mass spectrometry to measure the levels of these proteins, which are usually present at low levels in the blood and are very similar to each other. The researchers emphasize that the study demonstrates association and that research of studies over time would be needed to predict risk. However, the results are the first step toward developing tests to predict risk of AMD and potential treatments. While elevated levels of each of the five FHR proteins is associated with AMD risk, the inflammation pathway is not the only driver of AMD. Therefore, being able to measure levels of these proteins would help to identify patients who would best benefit from FHR-targeting therapies.

My rating of this study: ⭐⭐

Cipriani V, Tierney A, Griffiths JR, et al. "Beyond factor H: The impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations." American Journal of Human Genetics.  13 July 2021. https://doi.org/10.1016/j.ajhg.2021.05.015