No procedure, transplant or drug can consistently thwart macular degeneration, the leading cause of blindness after age 55 in the industrialized world. A severe form of the disease, exudative or 'wet' macular degeneration, occurs when leaky blood vessels develop in a region beneath the retina and damage it. In the 4 March Proceedings of the National Academy of Sciences, Bora et al. deal a blow to exudative macular degeneration, demolishing the network of damaging blood vessels in pigs and mice.

Credit: Reprinted from PNAS

The investigators modeled the disease by inducing vessel growth by injuring the retina with a laser. Shown is a confocal image of a whole-mount mouse retina focused on an area of damage; vessels are shown in green and elastin, a component of connective tissue, in red.

The investigators destroyed the new vessels with a molecule called an 'Icon', targeted at tissue factor, a protein expressed on the new vessels. The Icon is composed of the natural ligand for tissue factor conjugated to the Fc domain of an IgG1 molecule. The tissue factor–Icon complex activates a potent immune attack that destroys the blood vessels after they have formed (inset, retina of treated mouse). The investigators examined over 60 damaged retinal areas and found that the incidence of new blood vessel formation decreased from 97% to 5% after injection with a vector encoding the Icon. Results were similar when the Icon was injected intravenously or directly into the eye.

Tissue factor is not expressed on normal vasculature, and the animals seemed to suffer no side effects. The method, which has shown success in cancer treatments, has the potential to outshine another experimental approach aimed at preventing vessel growth with anti-angiogenic steroids and other treatments. That's because the Icon acts on vessels that have already formed, which is when most cases of exudative macular degeneration are diagnosed.