Intrinsic eye protein halts angiogenesis

October 18, 2006

LEXINGTON, Ky. (Oct. 18, 2006) − Dr. Jayakrishna Ambati, of the University of Kentucky, and Dr. Balamurali Ambati, of the Medical College of Georgia, have jointly published a paper in the journal Nature detailing major research discoveries in corneal avascularity and angiogenesis.

In their paper published online Oct. 18, 2006, the researchers present evidence that unravels the mystery of how a healthy cornea remains clear and free of blood vessels, which is essential for vision, and raises questions about the implications for anti-angiogenesis treatments in macular degeneration, cancer and other diseases.

Angiogenesis, or blood vessel growth, is what propels the growth of cancerous tumors and blinding conditions like macular degeneration. Because healthy corneas are avascular (free of blood vessels) they have long been the testing grounds for anti-angiogenesis drugs intended to treat conditions in other areas of the body.

The Ambatis, brothers who are both engaged in the clinical practice of ophthalmology as well as in basic research, discovered that a protein known as SFLT-1 is singularly responsible for warding off blood vessel growth in the cornea. When SFLT-1 is deactivated, angiogenesis begins and blood vessels spontaneously invade the cornea. They studied a wide variety of mammals and confirmed the effect in each species including humans.

"The millenia-old mystery of corneal avascularity has been the subject of serious scientific inquiry for 50 years. The significance of this publication is that we have now identified a single protein responsible for this phenomenon, and it can be applied to other areas of the body as well," said Jayakrishna Ambati.

Previously, scientists had experimented with various ways to clear blood vessel growth in corneal tissue - a condition that often occurs due to herpetic infections of the eye, chemical burns, traumatic injury or surgery such as corneal transplantation.

"The standard paradigm has been the cornea is avascular because it has lots of anti-angiogenic molecules and it does," Balamurali Ambati said. "But knockdown of any of the other molecules does not cause blood vessels to enter the cornea. Knocking down SFLT-1 allows angiogenesis to take hold."

The next step, according to the researchers, is to test SFLT-1 in other areas of the body, encouraging tissues to produce the protein on their own.

"We want to know what it is in the cornea that produces so much of this protein which inhibits angiogenesis. With that knowledge we will be closer to fighting the growth of everything from vision-obscuring blood vessels in the eye to cancers," said Jayakrishna.
-end-
The article "Corneal Avascularity is due to soluble VEGF receptor-1" appears in the Oct. 26, 2006 print edition of Nature. It is currently available online at http://www.nature.com/nature/journal/vaop/ncurrent/index.html.

University of Kentucky

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