Angiopoietin-1 guides directional angiogenesis through integrin αvβ5 signaling for recovery of ischemic retinopathy

Junyeop Lee, Kyung Eun Kim, Dong Kyu Choi, Jeon Yeob Jang, Ji Jung Jung, Hiroshi Kiyonari, Go Shioi, Woohyok Chang, Toshio Suda, Naoki Mochizuki, Yoshikazu Nakaoka, Issei Komuro, Ook Joon Yoo, Gou Young Koh

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR) are ischemic retinal diseases caused by insufficient vascular network formation and vascular regression in addition to aberrant angiogenesis. We examined the role of angiopoietin-1 (Ang1) in retinal vascular network formation during postnatal development using Ang1 gain- and loss-of-function mouse models, and tested the effects of intraocular administration of Ang1 in an oxygen-induced retinopathy (OIR) mouse model that mimics cardinal features of ROP and PDR. We observed that Ang1 plays a substantial role in the formation of the retinal vascular network during postnatal development and that Ang1 supplementation can rescue vascular retinopathies by simultaneously promoting healthy vascular network formation and inhibiting subsequent abnormal angiogenesis, vascular leakage, and neuronal dysfunction in the retinas of the OIR model. We attribute these Ang1-induced effects to a dual signaling pathway - Tie2 signaling in the vascular region and integrin αvβ 5 signaling in the astrocytes. The activation of integrin αvβ5 signaling promoted fibronectin accumulation and radial distribution along the sprouting endothelial cells, which consequently stimulated guided angiogenesis in the retina. These findings shed light on the role of Ang1 in the recovery of ischemic retinopathies such as ROP, PDR, and retinal vascular occlusive disease.

Original languageEnglish
Article number203ra127
JournalScience translational medicine
Volume5
Issue number203
DOIs
Publication statusPublished - 2013 Sep 18

ASJC Scopus subject areas

  • Medicine(all)

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