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  • Genetics and Age-Related Macular Degeneration

    Jan. 19, 2023

    Nearly two million Americans have advanced age-related macular degeneration (AMD), a leading cause of vision loss in the United States. This number is projected to more than double over the next two decades.

    Anyone can develop AMD, but lifestyle, age,diet, and genetics are major factors in an individual's risk. It's clear that genetic factors have a significant influence on when AMD might start and how it progresses in individual patients.

    Many Genes Influence Macular Degeneration Risk, But Two Stand Out

    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. 

    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. Several gene therapy treatments are currently being studied based on these genetic variants in the complement pathway.

    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.

    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 for Age-Related Macular Degeneration

    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. 

    While current research is focusing on inhibiting the complement pathway to find new treatments for patients with advanced nonexudative or dry AMD. There are numerous clinical trials underway and currently two agents are seeking Food and Drug Administration approval to slow down the aging changes seen in patients with advanced AMD. Among them, many studies are looking at specific genetic mutations highlighting the importance of genetics in the pathophysiology of AMD.

    Preventing Blindness from Age-Related Macular Degeneration

    We may one day have targeted therapies for AMD based on an individual’s genes and lifestyle. For now, there are several preventative steps people can take to lower their chances of developing AMD:

    If you have AMD, existing treatments, including vitamin supplements and medications, can be very effective.