Angiopoietin-1 Guides Directional Angiogenesis Through Integrin alpha(v)beta(5) Signaling for Recovery of Ischemic Retinopathy

Title
Angiopoietin-1 Guides Directional Angiogenesis Through Integrin alpha(v)beta(5) Signaling for Recovery of Ischemic Retinopathy
Author(s)
장우혁이준엽[이준엽]김경은[김경은]최동규[최동규]장전엽[장전엽]장지정[장지정]히로시 기요나리[히로시 기요나리]고 시오이[고 시오이]도시오 수다[도시오 수다]나오키[나오키]나카오카[나카오카]고무로[고무로]유욱준[유욱준]고규영[고규영]
Keywords
OXYGEN-INDUCED RETINOPATHY; DIABETIC-RETINOPATHY; RETINAL ASTROCYTES; CELL RESPONSE; VEGF; TIE2; FIBRONECTIN; PREMATURITY; EXPRESSION; RECEPTOR
Issue Date
201309
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Citation
SCIENCE TRANSLATIONAL MEDICINE, v.5, no.203
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 alpha(v)beta(5) signaling in the astrocytes. The activation of integrin alpha(v)beta(5) 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.
URI
http://hdl.handle.net/YU.REPOSITORY/28967http://dx.doi.org/10.1126/scitranslmed.3006666
ISSN
1946-6234
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의과대학 > 안과학교실 > Articles
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