Researchers' discovery could improve diagnosis and lead to new treatments for AMD

Posted: Friday 07 February 2020

Researchers have identified a new protein linked to age-related macular degeneration (AMD) that could offer new hope for the diagnosis and treatment of the disease.

The research team, made up of scientists from Queen Mary University of London, the University of Manchester, Cardiff University, and Radboud University Medical Center, Nijmegen, found significantly higher levels of a protein called factor H-related protein 4 (FHR-4) in the blood of AMD patients.

Further investigation, using eye tissue donated to the Manchester Eye Tissue Repository, funded by the Macular Society, showed the presence of the FHR-4 protein within the macula. 

The results of this study open up new routes for the early diagnosis, by measuring FHR-4 levels in the blood, and suggests therapies targeting this protein could provide promising future treatment options for the disease.

FHR-4 regulates the complement system, part of the immune system, which plays a critical role in inflammation and the body’s defence against infection.

Previous studies have linked the complement system to AMD showing that genetically inherited faults in key complement proteins are strong risk factors for the condition.

In this study, the researchers used a genetic technique, known as a genome-wide association study, to identify specific changes in the genome related to the increased levels of FHR-4 found in AMD patients.

They found higher blood FHR-4 levels were associated with changes to genes that code for proteins belonging to the factor H family, which clustered together within a specific region of the genome. The identified genetic changes also overlapped with genetic variants first found to increase the risk of AMD over 20 years ago.

Together, the findings suggest that inherited genetic changes can lead to higher blood FHR-4 levels, which results in uncontrolled activation of the complement system within the eye and drive disease.

Blood levels of FHR4 were measured in 484 patients and 522 age-matched control samples using two independent, established collections of AMD patient data, the Cambridge AMD study, led by Professor Anthony Moore from Moorfields Eye Hospital and UCL Institute of Ophthalmology (now at the University of California San Francisco) and Professor John Yates from Cambridge University, and the European Genetic Database (EUGENDA), led by Professor Anneke den Hollander and Professor Carel Hoyng from Radboud University Medical Center.

Professor Paul Bishop, an ophthalmologist and AMD expert at the University of Manchester, added: “The combined protein and genetic findings provide compelling evidence that FHR-4 is a critical controller of that part of the immune system which affects the eyes. Apart from improving understanding of how AMD is caused, this work also provides a way of predicting risk of the disease by simply measuring blood levels of FHR-4 and also provides a new route to treatment by reducing the blood levels of FHR-4 to restore immune system function in the eyes.”

Geraldine Hoad, research manager at the Macular Society, said: “While still in its early stages, this is a promising discovery which may result in a new route of diagnosis through blood tests and could potentially lead to new treatments for patients living with AMD. We welcome any research which could provide hope to patients diagnosed with macular disease.”

This exciting research was made possible by the Manchester Eye Tissue Repository, which was set up thanks to the generous help of our supporters including the Sir Samuel Scott of Yews Trust, the Chapman Charitable Trust, The Mabs Mardulyn Charitable Foundation and The Inman Charity.