BioEd Online

Geneticists have pinpointed a mutation that increases the chances of age-related blindness. The discovery, made by three separate research groups, could help to identify people who are most vulnerable to the condition.

Age-related macular degeneration (AMD) is the chief cause of blindness among the elderly in the developed world, affecting more than 10 million people in the United States alone. The condition involves the deterioration of the central part of the retina, the 'macula', leading to problems distinguishing colours and seeing motion. It ultimately blots out central vision completely.

Spotting those most at risk would help to ensure they receive preventative treatment. Although there is no cure, the condition can be slowed by using lasers or drugs to stop damaged, leaky blood vessels from proliferating.

The causes of AMD are complicated with experts suspecting the involvement of many factors, both genetic and environmental. Smoking and obesity, for example, are both risk factors.

But this picture may not be quite as complex as many had feared, says Albert Edwards of the University of Texas Southwestern Medical Center in Dallas, who led one of the three studies. His team and two other teams have independently pinned down a simple genetic change that could explain around 50% of the variation between people who develop AMD and those who don't.

Complementary change

The change is in a gene that produces an immune protein called complement factor H (CFH). The single-letter difference in the gene's DNA sequence increases a person's chance of developing AMD by a factor of around three, Edwards and his colleagues report in Science¹.

CFH plays a part in the inflammatory response, Edwards explains. The single-letter change in the gene, which leads to a tiny change in the protein's sequence of amino-acid building blocks, may cause excessive inflammation that ultimately destroys cells in the macula and causes blindness, he suggests.

Two other groups, also reporting their findings in Science, made an almost identical discovery by studying genetic sequences from blind and healthy volunteers. One team was led by Josephine Hoh of Yale University School of Medicine in New Haven, Connecticut²; the other was headed by Margaret Pericak-Vance of Duke University Medical Center in Durham, North Carolina³.

The fact that three groups all made the same discovery adds to its credibility, says Pericak-Vance. "It's more of an overwhelming statement of 'yes it's right'," she says.