Mutant genes trigger AMD but may lighten the way to new treatments

Mar 7 2006

According to new research in the U.S., the most common form of blindness in the elderly, age-related macular degeneration (AMD), can be attributed to just two genes which trigger the condition.

The scientists say that as many as three out of four patients with AMD have mutations in one or both key genes.

AMD affects one in ten people aged over 60 in the U.S. and 74 per cent of patients with the disabling condition apparently have such genetic mutations.

Macular degeneration causes the gradual loss of sight due to damage to the macula, a very sensitive area in the centre of the retina that is responsible for fine and detailed vision.

Although only central vision is lost initially, the disease can cause total blindness.

The scientists believe the discovery could lead to new ways to treat diminishing sight and may suggest new targets for drugs that might slow or even prevent the progressive damage to the retina that occurs in AMD.

As many as 50 million people worldwide are estimated to be irreversibly blinded by the condition.

Research has revealed that many single-gene disorders are caused by one mutation, such as Huntington’s disease or cystic fibrosis, but it remains unclear to scientists what triggers many other conditions, in which more than one mutation is involved.

Professor Rando Allikmets, of Columbia University in New York, the lead researcher, says he does not know of any other complex disorder where nearly 75 per cent of genetic causality has been identified.

Experts have been aware for a long time that there is a hereditary factor with a clear genetic component in AMD, but recent research has linked several variants of a gene known as Factor H to an increased risk of developing AMD.

Factor H produces a protein that helps to shut down the immune response to bacterial or viral infections once the invading pathogens have been eliminated, preventing damage to healthy tissue.

The mutated versions appear to cause extended inflammation that can harm the retina.

The Factor H gene alone only explains between 30 and 60 per cent of AMD cases, and a third of people with the apparently harmful mutation do not develop the disease.

This led the Columbia team, which identified the role of Factor H, to seek other genes that might play a part.

In a new genetic analysis of some 1,300 people a second gene, known as Factor B, has also has been found to have a significant effect on AMD.

Factor B is the mirror image of Factor H, starting rather than stopping the immune response, and certain variants appear to protect the eye when a person has a harmful Factor H mutation.

The research suggests that between the two of them, Factor H and Factor B account for 74 per cent of AMD cases.

The research explains much of the genetic risk, but the specific triggers that set off the immune response and subsequent inflammation are still unknown.

The research team, which includes scientists from the University of Iowa, are now looking for viruses and bacteria that might be the culprits.

The research is published in the journal Nature Genetics.