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Inflammation Gone Wild Can Lead To Macular Degeneration

Discovery May Lead To New Treatments

October 7, 2011

Summary: An international team of scientists, including a BrightFocus-supported researcher from Johns Hopkins, has determined how the immune system can go out of control and cause age-related macular degeneration (AMD) due to a single mutation in the complement factor H (CFH) protein.

The body responds to stressors, like invading pathogens, cigarette smoke, and sunlight, by turning on the immune system to flush out the toxins created by this “oxidative stress.”  CFH then “applies the brakes” to the typical inflammation response, keeping it under control. However, these researchers found that a single mutation in CFH destroys its ability to bind to certain markers of oxidative stress and disables its ability to function normally, leading to out-of-control inflammation, drusen deposits (consisting of fats, proteins, pigments, and other waste products), and AMD. “This molecular mechanism explains why the 'misbehavior' of the innate immune system predisposes to AMD susceptibility and points to an important role of oxidative stress in the pathogenesis of AMD,” says Dr. Hendrik Scholl from the Wilmer Eye Institute,  Johns Hopkins University, who is co-author of the paper.

Relevance: This study has provided an explanation for how a mutation in the CFH gene is associated with oxidative stress, inflammation, retinal drusen deposits, and the increased risk of AMD. In the future, this discovery could lead to new treatments for the millions of people who suffer from this disease.

On behalf of our donors, Macular Degeneration Research—a program of the BrightFocus Foundation—salutes grantee Dr. Hendrik Scholl and his collaborators for this important work.

Co-author Dr. James Handa is a former BrightFocus grantee.


  • Original publication (October 6, 2011): http://www.nature.com/nature/journal/v478/n7367/full/nature10449.html

    “Complement factor H binds malondialdehyde epitopes and protects from oxidative stress,” David Weismann, Karsten Hartvigsen, Nadine Lauer, Keiryn L. Bennett, Hendrik P. N. Scholl, Peter Charbel Issa, Marisol Cano, Hubert Brandstätter, Sotirios Tsimikas, Christine Skerka, Giulio Superti-Furga, James T. Handa, Peter F. Zipfel, Joseph L. Witztum & Christoph J. Binder  (2011) Nature 478: 76–81
  • Nature News & Views article highlighting the  original publication (October 6, 2011): http://www.nature.com/nature/journal/v478/n7367/full/478042a.html

    “Molecular medicine: Defence against oxidative damage,” Fernando Cruz-Guilloty and Victor L. Perez. (2011) Nature 478: 42–43


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Disclaimer: The information provided in this section is a public service of the BrightFocus Foundation, and should not in any way substitute for the advice of a qualified healthcare professional, and is not intended to constitute medical advice. Although we take efforts to keep the medical information on our website updated, we cannot guarantee that the information on our website reflects the most up-to-date research. Please consult your physician for personalized medical advice; all medications and supplements should only be taken under medical supervision. BrightFocus Foundation does not endorse any medical product or therapy.

Some of the content in this section is adapted from other sources, which are clearly identified within each individual item of information.

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