UK researcher finds 'switching' compound for angiogenesis

February 02, 2006

LEXINGTON, Ky. (Feb. 2, 2006) − For the second time in a week Dr. Jayakrishna Ambati, UK HealthCare physician and associate professor and vice chair of the Department of Ophthalmology and Visual Sciences, announced a discovery from his lab that will affect the future of macular degeneration treatment and research.

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.

These surprising findings have far-reaching implications beyond ophthalmology and into all areas of medicine because angiogenesis is also the process by which other growths spread in the body, including malignant tumors. Ambati's work has opened the door into methods of controlling angiogenesis and its effects.
Ambati's paper can be found in the current issue of the Journal of Clinical Investigation. The PDF of the full article may be downloaded from

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