Preventing pathological regression of blood vessels.

Abstract

A number of human disorders are associated with obliteration of preexisting blood vessels. Microvessel rarefaction often takes place in the hypertensive lung, in the myocardium of patients with chronic renal failure, and in the elderly. Conversely, a failure to eliminate transient embryonic vasculature destined for regression may lead to a disease, as exemplified by the common congenital developmental anomaly of the eye, persistent hyperplastic primary vitreous, in which hyaloid vessels fail to regress. A striking example of a disease caused by vessel regression is retinopathy of prematurity (ROP). ROP is a blindness-causing neovascularizing disease that affects premature infants treated with high concentrations of oxygen. ROP develops in two distinct stages. First, the hyperoxic insult leads to obliteration of immature retinal vessels, thereby compromising retina perfusion. The second phase, initiated upon resumption of the breathing of normal air, is an adverse compensatory neovascularization response, mediated by ischemia-induced VEGF, in which formation of new vessels is excessive, neovessels are leaky, and the inner limiting membrane of the retina is breached, allowing vessel growth into the vitreous. The later event may ultimately lead to retinal detachment and vision loss.