Project 172044

Retinopathy of prematurity (ROP) is the major serious eye disorder of the child. This condition is associated with long term complications, including strabismus, myopia, abnormal color discrimination, and blindness. ROP evolves from a relatively high extrauterine oxygen exposure of the premature child, which results in arrest in vascular development and degeneration of present vasculature. This anomaly leads to an excessive attempt of the tissue to repair itself, leading to abundant neovascularization that penetrates the vitreous, and predisposes to hazardous retinal detachment. Our laboratory has identified numerous mediators that cause vascular degeneration and new ones that are proliferative. However, to date the mechanisms that unable vessels to reform in vascular depleted areas are unknown. If one would identify these factors, desirable therapies can be envisaged. We therefore set out to begin to tackle this challenge and have identified a notable candidate, namely protease-activated receptor type 2. Activation of this receptor restores vascularity of the vascular depleted areas of the retina in ROP models. This important pilot information sets the basis of our current grant application, and opens the door for readily amenable therapeutics, superior to currently utilized ones.