Reparative angiogenesis in ischemic retinopathy

Retinopathy of prematurity (ROP) is the leading cause of blindness in the U.S. and other developed countries in the pediatric population. A pivotal aspect of early ROP is retinal avascularity, which leads to advanced stages of ROP and pathologic retinal NV. Deficiency in vascularization of ischemic tissue is a major challenge in this disease condition. Current treatments for ROP are largely focused on later stages of disease characterized by pathologic pre-retinal neovascularization. These treatments are associated with significant side effects and do not address the retinal avascularity, which has an impact on the patient’s ultimate visual function. There is great need for early treatment, directed toward the promotion of “physiologic” retinal vascularization (i.e., vascularization of the avascular/ischemic retina), which would relieve retinal hypoxia, leading to resolution of pathologic neovascularization and optimizing visual function. Although revascularization of ischemic retina (reparative angiogenesis) is a highly desirable objective in ROP, accomplishing this objective has posed a significant challenge. In this respect, there is a great need for better understanding of the cellular mechanisms regulating reparative angiogenesis, as well as for treatment strategies. It has been especially elusive why endothelial cells fail to vascularize the ischemic retina and instead grows into the preretinal space. In order to fully realize the goal of promoting reparative angiogenesis, it is critical to better understand how to promote endothelial cells toward revascularizing the ischemic retina, especially in identifying important angiogenic regulators. We have identified a novel molecular mechanism regulating the angiogenic phenotype of retinal endothelial cells. This project will examine the functional role of this angiogenic regulator in endothelial cell activity and dissect mechanisms of its angiogenic regulation. This project could thereby lead to insights into a new target for treatment and develop therapeutic strategies for revascularization that could be beneficial for ROP and other ischemic retinal diseases.