RetGen

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.

Vascular endothelial growth factor (VEGF) is a substance that promotes angiogenesis - the formation of new blood vessels from pre-existing vessels. In macular degeneration, vessels grow through angiogenesis, destroying the cells that are required for vision. Scientists have long believed that turning off the source of VEGF would lead to halting angiogenesis and disease progression.

Ambati's lab found that while withdrawing VEGF could halt angiogenesis in some areas, it actually encouraged it in others. Upon further investigation Ambati found that this previously undiscovered anti-angiogenic effect of VEGF was mediated via activating VEGFR-1 (VEGF receptor 1) and deactivating VEGFR-2 (VEGF receptor 2). Additionally, his lab found that a compound known as SPARC (secreted protein, acidic and rich in cysteine) could influence and switch the routing of VEGF away from VEGFR-1. Thus, controlling SPARC levels appears to be key to controlling angiogenesis in macular degeneration.