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Biological Chemistry

The Answer Is Clear

Growth factor receptor is found to keep the eye's cornea free of blood vessels

by Ann M. Thayer
July 19, 2006 | APPEARED IN VOLUME 84, ISSUE 30

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Researchers believe the VEGFR-3 protein in the cornea's epithelium acts as a sink for growth factors and prevents blood vessel development.
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Researchers believe the VEGFR-3 protein in the cornea's epithelium acts as a sink for growth factors and prevents blood vessel development.

If you have ever wondered why only the whites of your tired eyes are bloodshot, Harvard Medical School researchers believe they have the answer. Understanding what keeps the clear cornea covering the front of the eye free of blood vessels is to understand what makes vision possible. If the cornea weren't clear, light couldn't pass to the heavily vascularized back of the eye for processing.

Blood vessel formation abruptly stops at the cornea due to high levels of vascular endothelial growth factor receptor-3 (VEGFR-3) in the top epithelial layer of a healthy cornea, concludes the team from medical school affiliates Schepens Eye Research Institute and the Massachusetts Eye & Ear Infirmary, along with collaborators at biotech company ImClone Systems (Proc. Natl. Acad. Sci. USA 2006, 103, 11405). The team was led by Schepens senior scientist Reza Dana.

On the basis of a series of experiments, they believe VEGFR-3 halts angiogenesis (growth of blood vessels) by binding growth factors that would otherwise stimulate the process. In most tissues, these growth factors help increase blood flow to heal an injury or fight infection.

According to the researchers, it's long been known that the cornea doesn't have blood vessels; cartilage is the only other tissue that is also free of them. Previous studies have suggested reasons why, including other antiangiogenic factors and VEGF receptors. "To date, no single factor has been identified as being critically responsible" for keeping the cornea free of blood vessels, they note.

Understanding the mechanism holds promise for preventing and curing certain eye diseases and possibly controlling abnormal or uncontrollable blood vessel growth in other tissues as occurs in cancers, the researchers suggest. ImClone has a research program under way on VEGFR-3 antagonist antibodies to inhibit tumor growth and metastasis.

The researchers conducted experiments using corneal tissue from mice to test their hypothesis. First, they detected both the VEGFR-3 gene and receptor in the epithelial layer. A comparison of injured corneas with and without epithelial layers showed that blood vessels developed only in the latter. And in corneas with epithelial layers, they were able to suppress blood vessel growth with a VEGFR-3 substitute or initiate it by blocking VEGFR-3's role as a growth factor trap.

"The results from this series of tests confirmed our belief that the presence of VEGFR-3 is the major factor in preventing blood vessel formation in the cornea," Dana concludes.

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