Vascular Endothelial Growth Factor

Edited by: Steven Benowitz KEY PLAYER: Lloyd Paul Aiello of the Joslin Diabetes Cener found that VEGF plays a crucial role in causing retinal disease. L.P. Aiello, R.L. Avery, P.G. Arrigg, B.A. Keyt, H.D. Jampel, S.T. Shah, L.R. Pasquale, H. Thieme, M.A. Iwamoto, J.E. Park, H.V. Nguyen, L.M. Aiello, N. Ferrara, G.L. King, "Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders," New England Journal of Medicine, 331:1480-87, 1994. (Cited in more than 80 publications through October 1996) Comments by Lloyd Paul Aiello, Joslin Diabetes Center, Boston Some 125,000 new cases of diabetic retinopathy are diagnosed every year in the United States. The disorder, which can result in blindness, is characterized by a lack of oxygen reaching the retina, resulting in a proliferation of new blood vessel growth. This process, called angiogenesis, is common in many cancers and implicated in the growth and spread of many solid tumors, such as those in the breast, colon, and prostate. According to Lloyd Paul Aiello, a research associate at the Joslin Diabetes Center and an instructor in ophthalmology at the Harvard Medical School, diabetic retinopathy affects the retina's blood vessels-"they actually atrophy and seem to disappear, leaving areas of the eye's retina without a proper blood supply," he explains. The body attempts to circumvent this condition, known as ischemia, by growing new vessels. But these vessels don't grow back properly; they are fragile, frequently bleed, and cause retinal detachment. According to Aiello, no one knew the mechanism that controls this blood vessel growth, though growth factors were suspected. Previous work by other researchers indicated that vascular endothelial growth factor (VEGF), which is produced in the retina, is a likely contributor. Experiments in mouse retinal tumors showed high concentrations of VEGF in areas of low oxygen. In this paper, Aiello and his coworkers found evidence that VEGF may promote angiogenesis. VEGF, then, may be a target for future therapeutics for retinal disease. "We wanted to see if the levels of VEGF were elevated in patients with diabetic retinopathy" and in the predicted concentrations, he explains. "In 10 patients studied, the levels of growth factor were higher in the back of the eye than in the front, which is what was predicted." Next, they looked at the VEGF levels after corrective laser surgery to see if the concentrations were reduced. They obtained fluid from the eye in six patients before and after laser surgery for active disease. In all six, the VEGF levels were lowered. In a subsequent paper, Aiello and colleagues showed that inhibiting VEGF activity could suppress vessel growth in a mouse model of ischemic retinopathy (L.P. Aiello et al., Proceedings of the National Academy of Sciences, 92:10457-61, 1995). Aiello believes the New England Journal paper was cited so frequently because it is "the first major paper showing the correlation of active disease, this growth factor, and angiogenesis in humans." He also believes that the finding has major implications in potential treatments for diabetic retinopathy. "We might have a way of blocking vascularization without causing destruction of the retina, which is what happens now. We currently use laser therapy to destroy areas of the retina to help the vascularization regress." He predicts that manipulating VEGF levels "might have a potential role in treating difficult cases of eye disease, particularly where laser therapy is difficult-in an infant, for example. It [this work] might have implications for angiogenesis treatment for vascularized tumors, as well." The next step, Aiello says, is to develop chemical inhibitors that would block VEGF from promoting new blood vessel growth.

Vascular Endothelial Growth Factor

The Scientist Staff

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