What Causes Blindness?

A research breakthrough from the Queen Mary University of London could offer new insight into blindness, with the team identifying a protein linked to age-related macular degeneration (AMD), the leading cause of loss of vision. The disease affects mor than 1.5 million people in the UK, with the team hopeful the research could revolutionise diagnosis and treatment of AMD.

As well as researchers from Queen Mary University of London, the team also included scientists from Cardiff University, the University of Manchester and Radboud University Medical Centre in the Netherlands. After analysing the blood of patients diagnosed with AMD, the team found noticeably higher levels of factor H-related protein 4 (FHR-4), a protein that's thought to be a key molecular driver in blindness.

Regulating the complement cascade

The main role of FHR-4 is to regulate the complement cascade, a part of the immune system that promotes inflammation and amplifies the body's defence against infection by boosting the effectiveness of antibodies and phagocytic cells. They explored the role of FHR-4 further using eye tissue donated for medical research and found elevated levels of FHR-4 within the macula, the central area of the retina that's affected by AMD.

For the team, the results of the study could open new pathways for early diagnosis of age-related macular degeneration. By proactively measuring FHR-4 levels in the blood, they hope at risk patients could be identified and offered new therapies and treatment options.

Unlocking data with a genome-wide association study

To link the complement cascade to AMD, the team used a genetic technique called genome-wide association study. This allowed them to pinpoint unique changes in the genome that trigger increased levels of FHR-4. Overall, high levels of FHR-4 in the blood were linked to genetic changes that affect the coding of proteins in the factor H family. This suggests that inherited genetic changes can result in higher levels of FHR-4 in the blood, which in turn sends the complement cascade into overdrive and fast tracks age-related macular degeneration.

Dr Valentina Cipriani, Senior Bioinformatics Research Fellow at Queen Mary University of London says, "By unveiling FHR-4 as a novel, key molecular player for AMD, our study was able to dissect further the genetic disease predisposition at the factor H region. This is one of the most established genetic associations in the field of complex genetics. We hope our findings will accelerate interest from the wider research community in the involvement of the complement system in AMD, with the ultimate goal of uncovering the role of the whole 'complementome' in the disease."

From genome-wide association studies to native mass spectrometry (MS), science plays a critical role in advancing healthcare. For a glimpse of the latest breakthroughs from Thermo Fisher Scientific (UK) Ltd, head to 'Comprehensive Characterisation of Monoclonal Antibodies Using Charge Variant Analysis Coupled to High-Resolution Mass Spectrometry.'