Protein closely linked to commonest cause of blindness

February 07, 2020

An international team of scientists has identified a protein which is strongly linked to the commonest cause of blindness in developed countries when its levels are raised in the blood.

The discovery is a major step forward in the understanding of age-related macular degeneration, which affects 1.5 million people in the UK alone.

The study, carried out by the team from Universities of Manchester, Cardiff, London and Nijmegen, and Manchester Foundation NHS Trust is published in Nature Communications.

The major funder was the Medical Research Council.

The protein, called FHR4, was found by the team to be present at higher levels in the blood of patients with AMD compared to individuals of a similar age without the disease.

The findings were confirmed in 484 patient and 522 control samples from two independent collections across Europe.

Analyses of eyes donated for research after life also revealed the FHR4 protein was present in the AMD-affected parts of the eye

FHR4 was shown by the team to activate part of the immune system -called the complement system; over activation is a major causal factor of AMD.

FHR4 is one of a group of proteins that regulate the complement system and the genes encoding these proteins are tightly clustered on chromosome 1, the largest human chromosome.

When the team investigated a set of genetic variants across the human genome, they found that genetic variants in this region on chromosome 1 determined the levels of FHR4 in the blood. And they found that the same genetic variants were associated with AMD.

Professor Paul Bishop and Professor Simon Clark, from the University of Manchester were part of the leadership team on the study.

Professor Bishop, who is also a Consultant Ophthalmologist at Manchester Royal Eye Hospital, said: "The combined protein and genetic findings provide compelling evidence that FHR4 is a critical controller of that part of the immune system which affects the eyes.

"We have shown that genetically determined higher blood FHR4 levels leads to more FHR4 in the eye which in turn increases the risk of the uncontrolled immune system response that drives the disease.

"So apart from improving understanding of how AMD is caused, this work provides a way of predicting risk of the disease by simply measuring blood levels of FHR4.

He added: "It also provides a new route to treatment by reducing the blood levels of FHR4 to restore immune system function in the eyes.

"Because treatments options for AMD are limited, this comprehensive understanding of the biology of AMD is a huge boost for scientists finding answers to a problem which causes untold misery for thousands of people in the UK alone."

Professor Simon Clark, a specialist in the regulation of the complement system in health and disease said: "This study really is a step-change in our understanding of how complement activation drives this major blinding disease.

"Up until now, the role played by FHR proteins in disease has only ever been inferred. But now we show a direct link and, more excitingly, become a tangible step closer to identifying a group of potential therapeutic targets to treat this debilitating disease."
-end-
NOTES FOR EDITORS

A component of the study was also partially funded by the Macular Society and Fight for Sight

An embargoed copy of the paper "Increased circulating levels of Factor H Related Protein 4 are strongly associated with age-related macular degeneration" is available on request

Professors Bishop and Clark are available for interview

For media enquires contact:

Mike Addelman
Media Relations Officer
Faculty of Biology, Medicine and Health
University of Manchester
07717 881567

Subject of study: humans
Type of evidence: experimental
Type of study: peer reviewed

University of Manchester

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.