In most mammals, the cornea — the transparent part of the eye over the lens — has no blood vessels. This trait is obviously essential for optimal vision, but it also means the cornea is a useful experimental system for studying the factors that promote or inhibit the formation of blood vessels (angiogenesis). But why the cornea remains avascular despite the presence of the potent angiogenic factor VEGF-A and the proximity of other highly vascular tissues has remained unclear.

In this issue, B. K. Ambati et al. (Nature 443, 993–997; 2006) show that in the cornea a soluble receptor, called sflt-1, traps VEGF-A, stopping it from directing the formation of blood vessels. When the authors blocked expression of sflt-1 using a variety of approaches, they saw an increase in free VEGF-A and in corneal vascularization, demonstrating that sflt-1 maintains corneal avascularity.

Blood vessels form spontaneously in the corneas of certain mutant mouse strains, as well as in those of people who suffer from a condition known as aniridia as a result of a similar mutation. Ambati and colleagues show that in all these cases, corneal vascularization is accompanied by a deficiency in the expression of sflt-1. In the mice, injections of sflt-1 reduced the corneal vascularization.

The authors surveyed different mammalian species to see whether the close relationship between the presence of sflt-1 and an avascular cornea is evolutionarily conserved. Manatees (pictured) are the only known organism with uniformly vascularized corneas. They compensate for their impaired vision with highly developed sensory bristles that enable them to navigate and locate food. Manatees live primarily in turbid freshwater areas, and corneal vascularization may result from or protect against this environment. Interestingly, no sflt-1 expression was detected in manatee corneas, whereas those of dugongs (which belong to the order Sirenia, like manatees) and of elephants — the manatee's closest terrestrial relatives — all produced sflt-1.