It has long been appreciated that there is a deficiency in revascularization of ischemic retina even though there is robust pathologic neovascularization into the vitreous, a region of the eye normally devoid of blood vessels. Experiments by Joyal and colleagues suggest that ganglion cells in the avascular retina secrete Semaphorin 3A, which acts as a repulsive force against revascularization of the ischemic retina and directs neovessels toward the vitreous to form pathologic neovascular tufts. Professional illustration by Marie Dauenheimer.