University of Kentucky researcher identifies key to macular degeneration progression

Dr. Jayakrishna Ambati UK HealthCare physician and Associate Professor and Vice Chair of the Department of Ophthalmology and Visual Sciences, announced a discovery by his research team that will impact how physicians and patients approach treatment for macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of permanent vision loss among the elderly in many industrialized countries, including the United States. Approximately 15 million people in the U.S. have the early "dry" form of macular degeneration. Of those patients, about ten to 20 percent go on to develop the late-stage or "wet" form of the disease. The earliest clinical indicator of macular degeneration is the presence of drusen, or extracellular deposits that accumulate beneath the retinal pigmented epithelium.

Although science has known for some time that the presence of drusen is a risk factor for the development of late-stage AMD, it has been unclear whether or how drusen can provoke the development of the wet form of AMD.

Drusen in patients with AMD contain components known as complement C3 and C5. Ambati's lab has identified that bioactive fragments of these components, known as C3a and C5a, are present in patients whose AMD progresses beyond the early dry stage and into the later wet stage.

Ambati's research concludes that the presence of the C3a and C5a components in drusen are not only markers of AMD that will develop into the late-stage form of the disease, but that they are in fact causal. The presence of these components stimulates the progression of AMD. In the future, patients with early-stage AMD may be screened to determine if these effectors exist in their drusen. If they are present, then these patients could be considered at "high risk" for progression to advanced AMD.

The next step for Ambati's research is to develop a substance that can block the effectors, halting the progression of AMD from the dry to wet stages. His lab is already testing such substances that could potentially be used in patients with "high-risk" drusen.

Ambati's research, which was supported by the National Eye Institute, is published in the current issue of Proceedings of the National Academy of Sciences. More information is available at http://www.pnas.org/papbyrecent.shtml.

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