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Key to proper blood vessel growth in eye and ear discovered

gnal, recognized throughout the body, risks triggering unwanted blood vessel growth, perhaps feeding undetected tumors.

By contrast, the growth signal the Hopkins team identified seems to function only in the developing retina, where it promotes capillary formation, and in the inner ear, where it appears to help maintain the capillary network. It isn't known yet whether the signal is used later in life.

"Growth of blood vessels, like growth of nerves, must be precisely controlled, given the almost identical vascular anatomy from individual to individual," says Nathans. "What we learn about blood vessel growth in the eye may point to likely control systems in other kinds of cells."

Postdoctoral fellow Yanshu Wang, Ph.D., co-first author of the report, started the investigation by examining changes in mice missing Frizzled-4, which is defective in one form of familial exudative vitreoretinopathy, or FEVR (pronounced "fever"). She found that the mice had remarkably similar blood vessel problems in the eye and ear as seen in an earlier study of mice missing Norrin, which is faulty in Norrie [sic] disease. Both diseases are characterized by problems in blood vessel development in the retina; people with Norrie disease also go deaf over time.

Because of the similarities Wang found, co-first author and postdoctoral fellow Quiang Xu, Ph.D., examined whether the Norrin and Frizzled-4 proteins interact. He found that the two proteins bound each other selectively and strongly, and that Norrin caused efficient activation of the Frizzled-4 signaling pathway.

"The Norrie disease gene was found almost 12 years ago, but until now no one had been able to figure out what its product protein did or how it caused the disease," says Nathans. "Because the proteins behind the Norrie disease and FEVR are parts of the same process, these aren't two diseases, they are really two versions of the same disease."

The scientists also examined the
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
18-Mar-2004


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