The leading cause of irreversible vision loss in the United States is age-related macular degeneration (AMD). Nearly two million Americans have AMD.
This number is projected to more than double over the next 30 years.
Anyone can develop AMD, but lifestyle and diet are huge factors in an individual's risk. And it's clear that genetic factors have a lot of influence on when AMD might start and how it develops.
Large genome-wide association studies have identified over 30 genes associated with the risk of developing AMD. These kinds of studies look for genes that are more common in people with certain conditions. If a lot of people have a particular variation of a gene and also have a particular condition—while other people without the variation don't have the condition—that gene is said to be associated with the condition. Variants in all 30-plus of these genes contribute different levels of risk of developing AMD.
Variations in two genes have been more closely connected to both developing AMD and whether it progresses to the advanced stages of the disease. These are:
The presence of these genetic variants doesn't mean that someone will definitely develop AMD. These variants mean that one may have a higher risk of AMD or developing advanced disease in the future.
The complement cascade is an essential part of the body's immune system. It controls a series of proteins that protect against invading pathogens like bacteria and viruses. Complement can sometimes incorrectly target the body's healthy cells, including cells in the retina.
Some researchers believe that inflammation and immune mechanisms are part of what causes AMD. The connection between complement gene variants and AMD supports this theory. There are several variants of the complement genes, and they create different levels of AMD risk.
While scientists are intensively researching ARMS2/HTRA1, the role of these genes in AMD is not yet understood. It appears there is a strong connection, but we don't yet know what these genes do.
Other genes associated with increased AMD risk are involved in cholesterol and lipid (fat) metabolism, collagen production, DNA repair, protein binding, and cell signaling. Research on these genes and their role in disease onset and progression is still underway.
In addition, certain gene variants can have a protective effect against AMD, reducing an individual's risk of developing the disease. These include variants in other parts of the complement and immune gene groups, and other genes that affect lipids.
Genetic testing is available for some of the AMD risk genes. However, the American Academy of Ophthalmology does not currently recommend genetic testing for AMD. Gene therapy is not available for prevention or management of the disease, so there is no benefit of identifying which genes are involved in any individual's case of macular degeneration.
As future studies shed more light on AMD and individual genotypes—and if treatment tailored to individuals become available—genetic testing for AMD may become helpful. We may one day have targeted therapies for AMD based on the individual's genes and lifestyle.
In the meantime, anyone with a family history of AMD should have their eyes examined as recommended by an ophthalmologist, get enough exercise, eat a well-balanced diet and quit smoking. If you have AMD, existing treatments, including vitamin supplements and medications, can be very effective.