A protein (CFHR1) prevents an innate immune system from taking care to make inflammatory waste products harmless. This increases the risk of age-related visual disturbances (macular degeneration). Some people lack CFHR1 and their eyesight is less at risk. Antioxidant therapies could help the others, reports Viennese doctors in the journal “Pnas”.
Age-related macular degeneration affects around 200,000 people in Austria. From about 65 years of age, their eye power disappears at the spot of the keenest vision (macula) because toxic waste products (oxidation products) accumulate there and damage the retinal cells.
“One such waste product is malondialdehyde (MDA), which is found in abundance on dying cells and plays a role in age-related diseases such as macular degeneration, but also cardiovascular diseases,” explained Christoph Binder from the Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences (ÖAW) and the Clinical Institute for Laboratory Medicine at the Medical University of Vienna. In a previous study, he found that a “watchdog” of the innate immune system called “complement factor H” detains MDA, preventing it from causing inflammation.
Better risk assessment possible
In the current work, he and colleagues used blood serum samples from 2,000 people to test whether there are individual genetic differences that influence this binding of complement factor H to MDA. First, the doctors found out why a known genetic risk variant of the complement factor H can be found in many AMD patients: it affects the binding and thus reduces the protective function. They also discovered that a protein called CFHR1 can interfere with the official act of complement factor H: it also binds to the toxic waste product MDA, preventing complement factor H from holding onto it and performing its protective function against inflammatory reactions.
There are people who lack CFHR1, and epidemiological studies have known that they have a lower risk of age-related macular degeneration, Binder said. “Now you know why: If it is not there, more complement factor H can bind to the breakdown product and prevent inflammation.”
Now better risk assessments would be possible, whether someone has a higher or lower probability (predisposition) for such diseases. In addition, a therapy that is better tailored to the patient is conceivable: “With a certain constellation of genetic variants, taking antioxidants as a preventive measure could pay off,” says Binder. (apa)
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