Almost 2 million Americans have age-related macular degeneration (AMD), where the cells in the retina, which is the layer of tissue in the back of the eye, break down, causing central vision to become blurry. Over time, 100,000 of those will become blind.
An international team of scientists has identified a protein, FHR4, which is strongly linked to AMD when its levels are raised in the blood. The findings were confirmed in 484 patient and 522 control samples from two independent collections across Europe. 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.
Analyses of eyes donated for research after life also revealed the FHR4 protein was present in the AMD-affected parts of the eye and 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.
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.
"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," said Professor Paul Bishop from the University of Manchester. "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."