Angiogenesis, or the formation of new blood vessels, is a major component of a number of retinal and choroidal diseases, including proliferative diabetic retinopathy and age-related macular degeneration. For more than 50 years, researchers and clinicians have hypothesized about the pathogenesis of vessel proliferation. The establishment of techniques for culturing cells of the vasculature and neural retina, the identification and characterization of distinct angiogenic factors, and the development of the techniques of molecular biology have allowed significant insight into the cellular and molecular basis of choroidal and retinal microangiopathy.

In general, it is likely that growth of the microvasculature is regulated by a balance between local stimulators and inhibitors (Fig. 1). These growth-stimulating molecules include polypeptide growth regulators, such as vascular endothelial growth factor-vascular permeability factor (VEGF-VPF, hereafter referred to as VEGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), interleukin-8, insulinlike growth factor, and hepatocyte-growth factor (also known as scatter factor). These factors may exert their action in a soluble form, but some (for example, aFGF, bFGF, and VEGF) have been reported to be bound to heparan sulfate on the cell surface and in the extracellular matrix. Potential growth inhibitors include not only soluble factors such as transforming growth factor beta (TGF-/5), but also extracellular matrix constituents such as thrombospondin, which is reported to have antiangiogenic activity. 1 Although the factors involved in the control of angiogenesis are limited, there are numerous levels of control. For example, the synthesis of VEGF is regulated by the oxygen level in the microenvironment of the cells. bFGF may be controlled at a number of levels, including release and sequestration by heparan sulfate. On the other hand, the control of TGF-/0 appears to be not at the level of synthesis but, rather, through its activation. Thus, as would be expected, the critical process of angiogenesis appears to have multiple sites of regulation (Fig. 1).