Update on Genetics and Age-Related Macular Degeneration

Scheie Eye Institute, University of Pennsylvania
Wednesday, November 30, 2016
Graphic of a strand of DNA.

Age-related macular degeneration (AMD) is caused by a number of genetic and environmental factors. People with an affected parent have approximately twice the risk of getting the disease than someone whose parents do not have AMD. Learn about the genes that increase the risk of AMD, and whether genetic testing is recommended.

Recent advances in gene sequencing and mutation-detecting technology have identified sequence changes in at least 19 genes that can increase the risk.

Two Genes Stand Out

Two genes increase the risk of AMD more than any of the others. These are called complement and ARMS2/HTRA.

Complement is an arm of the immune system that attacks invading bacteria. It is a series of proteins that recognize the bacteria as foreign, then initiate a cascade of events that pokes holes in bacterial membranes and recruits white blood cells to kill them. Complement can sometimes inappropriately target our own cells, including those in the retina. Among the complement genes, complement factor H confers the greatest AMD risk.

Not only is complement genetically associated with AMD, it also has been shown to be activated in the retinas of people with AMD. The activated proteins were found near the cells that are damaged in AMD, within deposits called drusen. This has led researchers and pharmaceutical companies to develop complement inhibitors to treat or prevent AMD. In one phase II trial, a drug called lampalizumab, injected into the eyes of people with the advanced dry form of AMD called geographic atrophy, appeared to protect the retina by slowing the growth of atrophy. This drug has now entered larger, phase III clinical trials.

While ARMS2/HTRA is the subject of intensive research, the role of these genes in AMD is not yet understood. Other genes that confer AMD risk include those involved in cholesterol metabolism, collagen production, and cell signaling. Similarly, the research on these genes is not as advanced as it is for complement.

Genetic Testing

Genetic testing is now available to assess some of the AMD risk genes. Once the information from this testing is shown to affect the choice of AMD treatment, it could be helpful to undergo the testing.  For example, the lampalizumab phase II trial suggests that people with certain complement mutations may benefit from this treatment more than people without the mutations. If this result is reproduced in the phase III trial and lampalizumab becomes an FDA-approved drug, then genetic testing may become important.

However, currently there are no studies firmly demonstrating that genetic testing should influence AMD treatment selection. Anyone with a family history of AMD should see an ophthalmologist and try to eat a diet rich in fruits and vegetables, fatty fish twice a week (salmon, tuna, sardines, mackerel), avoid a high red meat diet, and avoid smoking.

The Future

As DNA sequencing technology becomes cheaper and faster (currently the whole genome can be sequenced in a few days for $1000!), and information about the meaning of DNA sequence changes is advanced, it is likely that genetic testing will be more practical and helpful in guiding treatments for AMD and a growing list of other diseases.

The information provided here is a public service of the BrightFocus Foundation and should not in any way substitute for personalized advice of a qualified healthcare professional; it is not intended to constitute medical advice. Please consult your physician for personalized medical advice. BrightFocus Foundation does not endorse any medical product, therapy, or resources mentioned or listed in this article. All medications and supplements should only be taken under medical supervision. Also, although we make every effort to keep the medical information on our website updated, we cannot guarantee that the posted information reflects the most up-to-date research.

These articles do not imply an endorsement of BrightFocus by the author or their institution, nor do they imply an endorsement of the institution or author by BrightFocus.

Some of the content may be adapted from other sources, which will be clearly identified within the article.

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