UC San Diego Shiley Eye Institute UC San Diego Shiley Eye Institute The Viterbi Family Department of Ophthalmology UC San Diego Shiley Eye Institute
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Afshari, Natalie A. Baxter, Sally L. Borooah, Shyamanga Brown, Stuart I. Camp, Andrew Do, Jiun Ferreyra, Henry A. Freeman, William R. Goldbaum, Michael H. Granet, David B. Haw, Weldon W. Heichel, Chris W. Huang, Alex A. Kikkawa, Don O. Kline, Lanning Korn, Bobby S. Lee, Jeffrey E. Liu, Catherine Y. Moghimi, Sasan Movaghar, Mansoor Nguyen, Thao P. Nudleman, Eric Puig-Llano, Manuel Robbins, Shira L. Rudell, Jolene Savino, Peter J. Scott, Nathan L. Spencer, Doran B. Toomey, Christopher B. Vasile, Cristiana Weinreb, Robert N. Welsbie, Derek S.
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New Treatments for Macular Degeneration

Angiogenesis involves the growth of new blood vessels, a process elemental to developing and sustaining life and health. However, there’s a dark side as well: some cancers exploit angiogenesis to feed tumors and spread disease. The phenomenon is not limited to just cancer.

Age-related macular degeneration (AMD) is the leading cause of blindness in older adults. There are two forms: “Dry” occurs slowly over time as portions of the retina atrophy. “Wet” is less common, but far more devastating. It is caused by abnormal, leaky blood vessel growth. While less than 20 percent of AMD cases are wet, they account for 80 to 90 percent of severe vision loss. Each year, roughly 200,000 new cases of wet AMD diagnosed in the United States.

Growing cancer tumors and wet AMD rely upon angiogenesis, but it was not until the 1990s and research by Napoleone Ferrara, M.D., that science was able to pinpoint the “X factor” that drives vascular growth, providing for the first time a therapeutic target for both cancer and AMD.


Dr. Ferrara was appointed during the past year as a Distinguished Professor of Ophthalmology and Pathology at the UC San Diego School of Medicine as well as the senior deputy director for basic science at UC San Diego Moores Cancer Center. In the 1980s, Ferrara, who had trained at the University of Catania Medical School in Italy, was working as a postdoctoral fellow at the UC San Francisco Medical Center, when he identified a protein that selectively promoted the growth of vascular endothelial cells – the cells that line the entire circulatory system, from the heart to the smallest capillaries. In 1988, he joined the South San Francisco-based biotechnology company Genentech. Ferrara and his colleagues at Genentech were able to isolate and clone this angiogenic molecule and termed it “vascular endothelial growth factor” or VEGF.

The discovery of VEGF proved a monumental advance. Since the protein was vital to growing blood vessels, researchers theorized that blocking the function of VEGF might deny tumors and wet AMD the sustenance needed to grow and spread. Ferrara and colleagues followed up with development of a humanized anti-VEGF antibody, the basis of the drug bevacizumab (Avastin), which has been approved for treatment of some forms of colorectal, lung and renal cancer, and subsequently used by ophthalmology for treating AMD and other retinal vascular diseases.

He also was focused on AMD, developing in his lab another anti-VEGF antibody fragment called ranibizumab (Lucentis) as a potential therapy for wet AMD. In 2006, the therapy was approved after multiple clinical trials showed substantial visual acuity gains in patients with severe cases. Ranibizumab has since been approved for treating retinal vein occlusion and diabetic macular edema as well as wet AMD.

“This work has been extremely gratifying,” said Ferrara, who continues to pursue AMD studies at the UC San Diego Shiley Eye Center. “I’m humbled by the magnitude of the benefit, particularly the improved vision in patients, which exceeded my expectations, considering that previous treatments only slowed down the rate of vision loss.”

In 2010, Dr. Ferrara won the prestigious Lasker-DeBakey Clinical Medical Research Award, often called the American Nobel Prize, for the discovery of VEGF as a major mediator of angiogenesis and the development of an effective anti-VEGF therapy for wet AMD. Most recently in February of this year, he received the inaugural Breakthrough Prize in Life Sciences for his discoveries in the basic mechanisms of angiogenesis that led to novel therapies for cancer and eye diseases.


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