Angiogenesis plays a pivotal role in the development of diabetic retinopathy and age-related macular degeneration, both of which are major causes of blindness. As these disorders progress, the blood vessels of the eye not only proliferate excessively, but the new vessels are weak and leaky and prone to hemorrhage. In both macular degeneration and diabetic retinopathy, new abnormal vessels bleed and cause blindness.

Anthony Adamis, M.D., in the Folkman lab discovered in the early 1990s, in collaboration with Dr. Lloyd Aiello (Joslin Clinic) and Joan Miller (current Chairman of Ophthalmology at the Mass Eye and Ear Infirmary) that vascular endothelial growth factor (VEGF), a naturally occurring angiogenic protein, is the critical factor in the development of new blood vessels in both diseases. By inhibiting VEGF, scientists hypothesized they could prevent the development of new blood vessels in the eye. Their hypothesis was borne out by subsequent research and, as a result, several anti-VEGF drugs are now in clinical trials for patients with these eye diseases.

Adamis discovered that the blockage and leaking in diabetic retinopathy occurs when leukocytes (white blood cells) adhere to the vessel wall. In collaborating with the pharmaceutical industry, they are using this knowledge to create new approaches to early detection and prevention. One project is the development of a non-invasive screening test of leukocyte adherence for people with diabetes. Another is the development of a drug to prevent leukocytes from adhering to vessel walls.

Researchers in the Folkman lab are simultaneously working on novel ways of delivering such drugs safely into the retina. They have developed a small device that could be implanted into a non-visible part of the eye. From there it would release the appropriate drug in a controlled fashion for 3-5 years, after which it could be replaced. Studies in animal models have demonstrated that this novel drug delivery strategy works. If clinical trials demonstrate that this approach is safe and effective in humans, it could also be used to deliver drugs for a range of eye diseases, and may become a vehicle for gene therapy as well.