Researcher Educates Capitol Hill About the Robo4 Protein Pathway During AMD Awareness Week 2009

Kang Zhang, M.D., Ph.D. discusses the dramatic implications of his AMD research

On September 22, the Alliance for Eye and Vision Research’s (AEVR) Decade of Vision 2010-2020 Initiative sponsored a Congressional briefing in recognition of International Age-related Macular Degeneration (AMD) Awareness Week 2009 (September 19-25), which was co-sponsored by the Congressional Vision Caucus, AMD Alliance International, the Association for Research in Vision and Ophthalmology (ARVO), Lighthouse International, and Prevent Blindness America (PBA).

Kang Zhang, M.D., Ph.D. , a professor of Ophthalmology and Human Genetics at the Shiley Eye Center (University of California at San Diego), spoke about his research into AMD, which is the leading cause of vision loss in older Americans. Nearly 25 million individuals age 50-plus have a high genetic risk of developing the disease, and an equal number currently experience early-to-advanced stages of the disease. About 600,000 AMD patients are newly diagnosed each year. Since AMD affects central vision, it severely affects a person’s ability to read and drive, which has an enormous impact on productivity, independence, and quality of life. With the aging of the population, AMD reflects a significant portion of the $68 billion annual cost to the United States of vision impairment and eye disease.

Research to date has demonstrated two major chromosome regions with the strongest association with AMD- the Complement Factor H (CFH) region, which is associated with the body’s immune response, and the HTRA1 gene. The risk of developing AMD can vary greatly, depending on whether an individual has one or both copies of the defective versions of these genes. Risk is further amplified by environmental factors, such as smoking and obesity. Through understanding the genetic risk, researchers can identify high risk populations and develop diagnostics and treatments, which could range from gene therapy (that is, inserting a "good" copy of the gene) to drug therapies that target the specific defect or pathway.

Dr. Kang’s research focuses on the role of Robo4, which is a protein found only in cells in the interior surface of blood vessels. Once the protein is activated, it initiates a chain of biochemical events to stabilize blood vessels and prevent uncontrolled growth. In the “wet” form of age-related macular degeneration (AMD), new blood vessels grow into a part of the retina (the light sensitive back of the eye) called the macula, which is necessary for central vision. These new blood vessels are often unstable and leak, affecting vision. In a March 2008 study published in Nature Medicine, a team of researchers led by Dr. Kang and Dean Li, M.D., Ph.D., (University of Utah), whose laboratory initially cloned the protein in 2003, reported that damage from AMD could be prevented or even reversed when the Robo4 protein was activated in mice models that simulated the disease, inhibiting abnormal blood vessel growth and stabilizing blood vessels to prevent leakage.

Dr. Kang’s research has used the same animal models required for drug development, meaning that the timeframe required to test treatments for AMD, as well as for diabetic retinopathy, could be shortened. "Our research is already looking at a small molecule approach to activate the Robo4 protein pathway, which could result in a minimally-invasive therapy to treat AMD, such as an eye drop or a pill," said Dr. Kang.

Dr. Kang’s research has been funded by the National Eye Institute (NEI) and the National Heart, Lung, and Blood Institute (NHLBI) within the National Institutes of Health (NIH). The NEI has described his work as "a prime example of basic science research yielding a discovery with direct clinical applications." He has also been supported by the private funding foundation Research to Prevent Blindness (RPB).

In introducing Dr. Kang, AEVR Executive Director James Jorkasky noted that he is the recipient of two grants funded through the American Recovery and Reinvestment Act (ARRA), which provided $10.4 billion in two-year stimulus funding to the NIH, $174 million of which to the NEI). His ARRA-funded NEI grants include a joint project with the Doheny Eye Institute/University of Southern California on the genetic basis of diabetic retinopathy in the Latino population and support for science teachers/summer students.

AEVR’s Decade of Vision 2010-2020 Initiative provides sustained education about the impact of eye disease and vision impairment. In House Resolution 366 and Senate Resolution 209 passed earlier this year, Congress designated 2010-2020 as the decade of vision and acknowledged the 40th anniversary of the NEI.

Dr. Zhang (right) was joined by representatives of briefing co-sponsor organizations, including from left Cynthia Stuen, Ph.D. (Lighthouse International) and Allie Laban-Baker (AMD Alliance International)	Dr. Zhang with Colonel Donald Gagliano, M.D., Director of the Vision Center of Excellence within the Department of Defense (DOD).
Dr. Zhang met with representatives of his work and home Congressional districts. Left image: AEVR’s James Jorkasky and Spencer Young (center) of the office of Cong. Susan Davis (D-CA). Right image: With Gary Kline of the office of Cong. Brian Bilbray (R-CA).