Grant: Project Grant

In disorders causing blindness, such as retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration (AMD), sprouting of new blood vessels (angiogenesis/neovascularization) that mainly occurs in the embryo leads to death of the nerve cells of the retina. These neovascular disorders place a substantial burden on patients and the health care system. AMD alone affects approx. 100,000 Canadians over the age of 50, while diabetic retinopathy is the most common cause of blindness in people under 65. Understanding the molecular basis of these diseases is the best hope for developing new medications to tackle them. Nerve cells in the retina require nutrients and oxygen provided by two distinct vessel beds: retinal vessels that support the optic nerve cells of the inner retina, and the choroid vessels that sustain the light-capturing photoreceptors of the outer eye. In neovascular eye disorders, the existing vessels sprout and new, leaky vessels extend within the vessels beds. The leakage leads to swelling in the eye that disrupts the nutrient and oxygen supply, and vision loss occurs as retinal cells degenerate. Current approaches to block new blood vessels from forming are not effective in all patients and they may have serious side-effects. We urgently need an effective way to prevent these faulty new blood vessels from forming, without affecting the health of retinal nerve cells or the normal blood vessels. This proposal addresses this gap by providing fundamental knowledge of a novel mechanism to prevent new blood vessels forming in the eye. We have identified a mechanism that normally controls eye vessel growth in the embryo that is implicated in pathological blood vessel growth in the adult eye. In this project we will define these mechanisms of normal and pathological eye blood vessel formation, informing the development of new treatments for neovascular eye disorders.