July 13, 1999 CHICAGO --- A protein found naturally in the healthy retina has been shown to halt excessive blood vessel growth in the eye and may one day be used as a treatment for diabetic retinopathy and macular degeneration, the leading causes of blindness in the Western world.
In an article in the July 9 issue of the journal Science, Noel Bouck and colleagues at The Robert H. Comprehensive Lurie Cancer Center of Northwestern University showed that the protein, called pigment epithelium-derived factor (PEDF), is the substance normally responsible for preventing blood vessels from entering two compartments of the eye through which light must pass -- the cornea and the vitreous -- thus helping to ensure clear vision.
Bouck, a professor of microbiology and immunology at Northwestern University Medical School, said this effect may have important therapeutic implications in both retinal tumors and in retinopathies where new blood vessel growth (angiogenesis) compromises vision and leads to blindness.
Bouck and her colleagues also found that the amount of PEDF produced by retinal cells is regulated by the amount of oxygen present, suggesting that a decrease in inhibitory PEDF provides a permissive environment for ischemia-driven angiogenesis in the retina that occurs in diabetic retinopathy.
These results raise the possibility that returning PEDF to its normal level in diabetic patients whose vision is deteriorating might prevent new vessels from overgrowing and leaking and thereby slow the clouding of their vision.
In healthy tissues, angiogenesis is tightly regulated by naturally occurring inhibitors that prevent new blood vessel growth. Disruption of this control results in excessive growth of new vessels that plays a major role in the development of many diseases, including arthritis and cancer.
It is possible that PEDF also may be useful in restoring control over vessel growth in these diseases. In laboratory studies performed by the Northwestern researchers, PEDF was found to be one of the most potent natural inhibitors of blood vessel growth discovered to date and to be effective against a broad range of angiogenic inducers.
Other researchers have shown that PEDF also promotes differentiation of the cells in retinoblastoma tumors, causing them to resemble non-dividing neurons.
"PEDF may have a double-barreled effect against retinoblastomas -- first, slowing their growth by binding to the endothelial cells that form new blood vessels and preventing the angiogenesis that the tumor needs and, second, binding directly to the tumor cells themselves, causing them to differentiate and thus grow more slowly," Bouck said.
This work grew out of a doctoral thesis project by M.D./Ph.D. student David W. Dawson and involved Olga V. Volpert, research assistant professor of microbiology-immunology; Paul Gillis, graduate student; and Susan E. Crawford, an assistant professor of pathology working at the Children's Memorial Institute for Education and Research, Northwestern University Medical School; as well as H.-J. Xu and W. Benedict, University of Texas, M.D. Anderson Cancer Center, Houston, Tex.
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