Key to proper blood vessel growth in eye and ear discovered
Scientists at the Howard Hughes Medical Institute at Johns Hopkins have uncovered the first cue to the carefully choreographed growth of tiny blood vessels in the eye and ear. Their report, in the March 19 issue of Cell, will help improve understanding of major eye diseases, most of which stem from abnormal blood vessel growth in the light-detecting retina.
The work also offers the first proof that nature has site-specific growth signals that could one day be exploited to treat a variety of diseases in which blood vessels -- or the need for new ones -- play important roles, such as in cancer, heart disease and stroke.
In their laboratory experiments, the research team discovered that two proteins linked to congenital blindness normally interact and signal blood vessels in the developing eye to branch into capillaries. The faulty versions found in people, however, don't interact correctly, preventing capillaries from forming and leading to either of two blinding diseases.
"Clearly, if you want to encourage blood vessel growth in a particular place, or stop it in a particular place, you'd have to use a specific signal or control production of a widely recognized signal only where and when it is needed," says Jeremy Nathans, M.D., Ph.D., a Howard Hughes Medical Institute investigator and a professor of molecular biology and genetics in Hopkins' Institute for Basic Biomedical Sciences.
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.
