Protein linked to commonest cause of blindness identified

An international team of scientists has identified a protein which is strongly linked age-related macular degeneration, the commonest cause of blindness in developed countries.

The protein, called FHR4, was found by the team to be present at higher levels in the blood of patients with age-related macular degeneration (AMD) compared to individuals of a similar age without the disease, according to a study published in the journal Nature Communications.

"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," said one of the researchers Paul Bishop, Professor at University of Manchester in Britain.

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

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.

The protein 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.

"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," Bishop said.

"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," he added.