By Liv Davies
Cardiff University researchers have been working with scientists from Queen Mary University of London, the University of Manchester, and Radboud University Medical Center, Nijmegen to identify a novel protein involved with age-related macular degeneration (AMD). This particular protein has been found to be significantly higher in patients with this disease.
Age-related macular degeneration occurs when cell products harmful to the macular accumulate, therefore causing the atrophy in this part of the eye that has a high concentration of photoreceptive cells. This can cause distorted or blurred vision, as well as a reduction in colour contrast.
The protein that was found to be significantly higher in patients with AMD is called FHR-4. The paper with these findings has recently been published in Nature Communications. There are hopes that targeting this protein could lead to new therapies being explored for AMD, which causes around 39,800 people to become visually impared in the UK alone. If targeting this protein proves not to be a viable solution for combatting AMD-related visual impairment, FHR-4 could act as AMD biomarker, and could therefore be used to assess if preventative measures need to be put in place to prevent visual impairment. Many environmental factors, such as high blood pressure, high cholesterol, and smoking can be risk factors to this disease. Furthermore, it is now known that a genetic predisposition to elevated FHR-4 levels contributes to an increased risk of AMD. With this new research, clinicians can now advise patients with raised levels of this protein to limit their environmental risk factors.
Professor Paul Morgan at Cardiff University led the development of assays that showed the elevated levels of FHR-4 were present in AMD patients. “The collaboration between experts in complement biology, eye disease and genetics across Europe has enabled the accumulation of a robust body of evidence that genetically dictated FHR-4 levels in plasma are an important predictor of risk of developing AMD.”
FHR-4 is a protein that is used in innate immunity. This type of immunity is different to that found in acquired immunity, which is the type that is utilised in vaccines. Innate immunity is used to fight general infections as well as control inflammation. Innate immunity uses the complement system, a cascade of proteins that is regulated by FHR-4 proteins, amongst others.
Through a technique called genome-wide association studies, the scientists at Cardiff along with other universities have identified areas of the genome that code for proteins that increase the production of FHR-4 in AMD patients. This results in over-activation of the complement system within the macular, and results in its degeneration.
Some types of AMD have had treatments associated with them, especially the faster or “wet” version of AMD. However the “dry” – or slower version of this disease has little to no treatments available. Before now, the complement system has only ever been implied in the progression of this disease. However it is now known that changes in the complement system via FHR-4 regulation can alter the development of AMD. This offers a different perspective in how we view this disease and its options for treatment. It is hoped that these scientific breakthroughs will help the thousands of patients living with this disabling disease to have a better quality of life.