Comparison of Bevacizumab and Aflibercept for Suppression of Angiogenesis in Human Retinal Microvascular Endothelial Cells

Author:

Yazdanyar Amirfarbod12ORCID,Cai Charles L.1,Aranda Jacob V.13,Shrier Eric3,Beharry Kay D.13ORCID

Affiliation:

1. Department of Ophthalmology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA

2. Retina Group of New England, Waterford, CT 06385, USA

3. Department of Pediatrics/Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA

Abstract

Bevacizumab (Avastin) is a vascular endothelial growth factor (VEGF) inhibitor that is widely used for aggressive posterior retinopathy of prematurity (APROP). Its use is associated with multiple adverse effects. Aflibercept (Eylea) is a VEGFR-1 analogue that is approved for ocular use, but its efficacy for APROP is less studied. We tested the hypothesis that Eylea is as effective as Avastin for suppression of intermittent hypoxia (IH)-induced angiogenesis. Human retinal microvascular endothelial cells (HRECs) were treated with Avastin and low- or high-dose Eylea and exposed to normoxia, hyperoxia (50% O2), or neonatal IH for 24, 48, or 72 h. Cells were assessed for migration and tube formation capacities, as well as biomarkers of angiogenesis and oxidative stress. Both doses of Eylea suppressed migration and tube formation in all oxygen environments, although the effect was not as robust as Avastin. Furthermore, the lower dose of Eylea appeared to be more effective than the higher dose. Eylea induced soluble VEGFR-1 (sVEGFR-1) coincident with high IGF-I levels and decreased Notch/Jagged-1, demonstrating a functional association. Given the role of VEGFR-1 and Notch as guidance cues for vascular sprouting, these data suggest that Eylea may promote normal vascular patterning in a dose-dependent manner.

Funder

Eunice Kennedy Shriver National Institute of Child Health & Human Development, Bethesda

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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