Researchers Identify Major Culprit in the Development of AMD

October 11, 2011

Though age-related macular degeneration (AMD) is a highly prevalent and blinding retinal disease affecting more than 10 million Americans, its cause has been a tough nut for researchers to crack, because of the multiple genetic and lifestyle factors that come into play. For decades, getting to the root causes of AMD has been challenging.

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But in a research paper published in the October 6, 2011 journal Nature, an international group of scientists, including the Foundation-funded investigator Dr. Hendrik Scholl from the Wilmer Eye Institute at Johns Hopkins Hospital, reported on an important research advance in overcoming the disease. They identified a faulty molecular defense mechanism — a mechanism that protects against damage from oxidative stress — as a major factor in AMD development. Most importantly, the discovery provides scientists with a new and clear target for developing better treatments.

The story of this advance actually began in 2005, when four other research teams, some of which included investigators funded by the Foundation, reported that certain variations in the gene Complement Factor H (CFH) significantly increased a person’s risk of developing AMD. They determined that detrimental variations in CFH were linked to as a many as half of all cases of the disease. It was, and continues to be, the strongest known genetic link to AMD.

While the science community knew that CFH was involved in controlling the innate immune system — a part of the immune system that fights off infection and other pathogens — they didn’t know exactly how or why certain variations in CFH increased AMD risk. A big question remained: What specifically does CFH do?

That question was answered when the international research group that included Dr. Scholl found that CFH led to the production of a protein that disarmed a prevalent, harmful byproduct of oxidative stress called malondialdehyde (MDA).

“The initial discovery of CFH’s link to AMD in 2005 was like identifying a major suspect in a crime. We had good evidence as to who the culprit was, but it wasn’t definitive proof,” says Dr. Stephen Rose, chief research officer of the Foundation. “But this latest finding on how defective CFH interacts with MDA was like witnessing the criminal in the act. Now we need to find a way from keeping the crimes from happening again.”

Oxidative stress occurs when the cells in our bodies can’t process and neutralize the overabundance of damaging byproducts, like MDA, that are caused by aging, unhealthy eating habits, smoking and other lifestyle and environmental stressors. By living healthfully, we have some control over oxidative stress. But a drug or biological therapy is needed to overcome the genetic factors that expose us to oxidative damage.

“This most recent advance gives us a clear target for helping to prevent and treat AMD at its root cause,” says Dr. Rose. “It also illustrates that good science is often incremental. It doesn’t happen overnight. But ultimately, the persistence pays off. And we need to remain persistent in moving forward.”