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.