Angiopoietin-1 in retinal angiogenesis and vascular remodeling

Abstract

Angiopoietin-1 (Ang1) is essential for embryonic vascular development and maintenance of vascular stability in adult, but little is known about the precise role of Ang1 in physiologic and pathologic angiogenesis in retina. I observed that Ang1 plays a coordinated role in proper formation and maturation of retinal vascular network during development. In addition, Ang1 supplementation into eyes with ischemic retina was able to rescue vascular retinopathies by simultaneously promoting healthy vascular network and reducing subse-quent pathologic angiogenesis and vascular leakage. As a result, Ang1-induced improved vascular integrity and function could prevent the retinal neurons from hypoxic damage. I attribute these Ang1-induced beneficial effects on ischemic retina to a dual signaling pathway- the combination of the Tie2 signaling pathway in endothelial cells, and the integrin αvβ5 signaling pathway in astrocytes that regulate fibronectin synthesis and radial distribution, which augments directional angiogenesis in the retina. These findings shed a light on the functional harmony that Ang1 brings forth through vascular Tie2 signaling and non-vascular integrin signaling for inducing healthy angiogenesis. Therefore, I suggest Ang1 supplementation as a potential treatment strategy for the fundamental vascular restoration of ischemic and permeable vascular retinopathies.