The normal retinal vasculature perfuses the macula of the neurosensory retina while avoiding interference with image resolution. The abnormal growth of blood vessels and associated bleeding and/or vascular leakage in retinopathy of prematurity (ROP), diabetics retinopathy (DR), exudative aged-related macular degeneration (AMD), and vascular occlusions are major causes of vision loss. Multiple cellular and soluble factors are involved in the formation, stabilization and regression of new retinal vessels. Among the cellular components, retinal astrocytes (RACs) play an important role in endothelial seeding of the primary retinal vasculature. However, the mechanism of astrocyte- endothelial cell interaction is incompletely understood. This proposal investigates a novel mechanism in which exosomes released by RACs target endothelial cells and result in normal retinal vasculature development. To test our hypothesis that molecules in RAC exosomes are important in the development of normal retinal vasculature, as well as the inhibition of aberrant retinal angiogenesis, we will 1) test the effect of exosomes from murine postnatal day 2 (P2) RACs (developing RAC exosomes) on proliferation, migration and tubule formation using retinal endothelial cells; 2) determine whether developing RAC exosomes can rescue aberrant angiogenesis induced by hypoxemia [i.e. oxygen-induced retinopathy (OIR)]; and 3) determine whether the angiogenic profiles of these exosomes reflect their function. Information derived from these results will further our understanding of the role of RAC exosomes in the development and maintenance of normal retinal vasculature. These observations may result in novel therapy to control aberrant retinal angiogenesis.
Normal retinal vasculature is critical for visual integrity. Any abnormality affecting vessel formation and regression during development or at later stages of life will lead to severe pathologies resulting in blindness, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and wet age-related macular degeneration (AMD). The goal of this application is to investigate a novel mechanism whereby exosomes released from retinal astrocytes (RACs) are involved in the development and maintenance of normal retinal vasculature and to explore a novel therapy to control abnormal retinal vasculature related diseases.
