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Anti-VEGF therapy in the management of retinopathy of prematurity: what we learn from representative animal models of oxygen-induced retinopathy

Authors Wang H

Received 1 October 2015

Accepted for publication 8 December 2015

Published 20 May 2016 Volume 2016:8 Pages 81—90

DOI https://doi.org/10.2147/EB.S94449

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Pachiappan Arjunan

Peer reviewer comments 2

Editor who approved publication: Professor Margaret Wong-Riley


Haibo Wang

Department of Ophthalmology, John A Moran Eye Center, The University of Utah, Salt Lake City, UT, USA

Abstract: Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness, affecting infants born prematurely. ROP is characterized by the onset of delayed physiological retinal vascular development (PRVD) and followed by pathologic neovascularization into the vitreous instead of the retina, called intravitreal neovascularization (IVNV). Therefore, the therapeutic strategy for treating ROP is to promote PRVD and inhibit or prevent IVNV. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of ROP. There is a growing body of studies testing the use of anti-VEGF agents as a treatment for ROP. Intravitreal anti-VEGF treatment for ROP has potential advantages compared with laser photocoagulation, the gold standard for the treatment of severe ROP; however, intravitreal anti-VEGF treatment has been associated with reactivation of ROP and suppression of systemic VEGF that may affect body growth and organ development in preterm infants. Therefore, it is important to understand the role of VEGF in PRVD and IVNV. This review includes the current knowledge of anti-VEGF treatment for ROP from animal models of oxygen-induced retinopathy (OIR), highlighting the importance of VEGF inhibition by targeting retinal Müller cells, which inhibits IVNV and permits PRVD. The signaling events involved in mediating VEGF expression and promoting VEGF-mediated angiogenesis, including hypoxia-dependent signaling, erythropoietin/erythropoietin receptor-, oxidative stress-, beta-adrenergic receptor-, integrin-, Notch/Delta-like ligand 4- and exon guidance molecules-mediated signaling pathways, are also discussed.

Keywords:
vascular endothelial growth factor, retinopathy of prematurity, intravitreal neovascularization, oxygen-induced retinopathy model, physiological retinal vascular development

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