Hypoxia-induced retinal neovascularization in zebrafish embryos: A potential model of retinopathy of prematurity
Journal
PLoS ONE
Journal Volume
10
Journal Issue
5
Pages
1298
Date Issued
2015
Author(s)
Abstract
Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression ? 2015 Wu et al.
Other Subjects
bevacizumab; cobalt chloride; messenger RNA; ranibizumab; semaxanib; vasculotropin A; vasculotropin receptor 2; messenger RNA; vasculotropin A; animal experiment; animal model; animal tissue; Article; blood vessel wall; controlled study; drug effect; embryo; gene expression; hypoxia; in vivo study; nonhuman; retina angiography; retina blood vessel; retina neovascularization; retrolental fibroplasia; signal transduction; vegfaa gene; vegfr2 gene; zebra fish; animal; disease model; hypoxia; larva; metabolism; neovascularization (pathology); newborn; pathology; retina; retina neovascularization; retrolental fibroplasia; vascular endothelium; Danio rerio; Animals; Animals, Newborn; Disease Models, Animal; Endothelium, Vascular; Hypoxia; Larva; Neovascularization, Pathologic; Retina; Retinal Neovascularization; Retinal Vessels; Retinopathy of Prematurity; RNA, Messenger; Vascular Endothelial Growth Factor A; Zebrafish
Publisher
Public Library of Science
Type
journal article