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February 8, 2000

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Scientists Identify Natural Chemical That Causes Blinding Blood Vessel Growth

Test Medications Stop the Process in Mice

A natural chemical substance the eye calls for backup when it's lacking oxygen is responsible for the blinding blood vessel growth that plagues patients with diabetic retinopathy, report researchers at Johns Hopkins and CIBA Vision Corp., a Novartis Ltd. Pharmaceutical Co.

The work verifies earlier studies suggesting the substance, called vascular endothelial cell growth factor (VEGF), is a key culprit in abnormal blood vessel growth. In studies of laboratory mice, the team has identified medications that block the actions of the substance, completely stopping the abnormal vessels from growing.

Results are reported in the February issue of the American Journal of Pathology.

VEGF is released by the retina (light-sensitive tissue in back of the eye) when normal retinal blood vessels are damaged by disease, causing an oxygen deficiency. VEGF turns on its receptor, a switch that ignites a chain reaction culminating in new blood vessel growth. However, these backup blood vessels are faulty; they leak, bleed and encourage scar tissue that detaches the retina, resulting in severe loss of vision. Such growth is the hallmark of diabetic retinopathy, the leading cause of blindness in young people in developed countries.

Several factors in addition to VEGF have been thought to contribute to abnormal blood vessel growth, so finding that blocking the receptor for VEGF is enough "is a pleasant surprise that bodes well for drug treatment of the process," says Peter A. Campochiaro, M.D., senior author of the study and a professor of ophthalmology and neuroscience at Hopkins.

"Despite evidence that multiple substances are involved in the creation of abnormal blood vessels in the retina, we now know that stopping one of them, VEGF, is enough to completely block the process," he says. "By designing drugs that specifically block VEGF receptors, it should be possible to stop abnormal blood vessel growth with fewer side effects."

In addition to causing growth of abnormal blood vessels, VEGF also causes normal blood vessels to become leaky. This leakiness underlies macular edema, another major cause of vision loss in diabetic patients. Macular edema occurs when fluid leaks out of vessels, resulting in thickening and distortion of the retina.

Clinical studies to determine if one of the drugs, called PKC 412, can stop abnormal blood vessel growth and prevent macular edema in patients with diabetic retinopathy are planned for April or May at Hopkins' Wilmer Eye Institute. A different type of abnormal blood vessel growth occurs in macular degeneration. Current studies are evaluating whether VEGF also plays a role in that process.

The study was supported in part by the U.S. Public Health Service; the National Eye Institute; Research to Prevent Blindness Inc.; CIBA Vision Inc.; Project Insight; the Association for Retinopathy of Prematurity and Related Diseases; and by private donors. The study's other authors were Hiroaki Ozaki, Man Seong So, Keiko Ozaki, Haruhiko Yamada, Eri Yamada and Naoyuke Okamoto of Hopkins; and Francesco Hofmann and Jeanette M. Wood of Novartis.

Campochiaro is a consultant to CIBA Vision Corp. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.

Related Web sites:

Wilmer Eye Institute at Johns Hopkins: http://www.wilmer.jhu.edu/
Dr. Campochiaro's laboratory: http://www.wilmer.jhu.edu/Campo/index.htm
Novartis Pharmaceuticals: http://www.novartis.com/
CIBA Vision: http://www.cibavision.com/
National Eye Institute: http://www.nei.nih.gov/
Research to Prevent Blindness, Inc.: http://www.rpbusa.org/
American Academy of Ophthalmology public information: http://www.aao.org/public/pi/

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