{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:18:25Z","timestamp":1787318305473,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,9,2]],"date-time":"2008-09-02T00:00:00Z","timestamp":1220313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Retinal neovascularization (NV) occurs in various ocular disorders including proliferative diabetic retinopathy, retinopathy of prematurity and secondary neovascular glaucoma, which often result in blindness. Vascular endothelial growth factor (VEGF) is an essential growth factor for angiogenesis, and is particularly regulated by hypoxia inducible factor\u20101\u03b1 (HIF\u20101\u03b1) under hypoxic conditions. Therefore, HIF\u20101\u03b1 and VEGF could provide targets for therapeutic intervention on retinal NV. In this study, we investigated the inhibitory effects of small interfering RNA (siRNA) targeting HIF\u20101\u03b1 and VEGF on the expression of HIF\u20101\u03b1 and VEGF in human umbilical vein endothelial cells (HUVEC) in vitro and on retinal NV in vivo. siRNA\u2010expressing plasmids targeting human HIF\u20101\u03b1 (HIF\u20101\u03b1 siRNA) and human VEGF\n                    <jats:sub>165<\/jats:sub>\n                    (VEGF siRNA) were constructed. They were transfected and co\u2010transfected to HUVEC and C57BL\/6J mice of ischemic retinopathy model. HIF\u20101\u03b1 siRNA and VEGF siRNA specifically downregulated HIF\u20101\u03b1 and VEGF at both mRNA and protein levels in vitro and in vivo. Neovascular tufts and neovascular nuclei were decreased in gene therapy group compared to control hypoxia group. Co\u2010transfection of HIF\u20101\u03b1 siRNA and VEGF siRNA resulted in maximal effects on VEGF suppression in vitro and in vivo. It also manifested the maximal inhibitory effect on retinal NV. These results indicate that the application of HIF\u20101\u03b1 siRNA and VEGF siRNA technology holds great potential as a novel therapeutic for retinal NV. J. Cell. Physiol. 218: 66\u201374, 2009. \u00a9 2008 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/jcp.21566","type":"journal-article","created":{"date-parts":[[2008,9,2]],"date-time":"2008-09-02T09:17:14Z","timestamp":1220347034000},"page":"66-74","source":"Crossref","is-referenced-by-count":65,"title":["Inhibition of retinal neovascularization by gene transfer of small interfering RNA targeting HIF\u20101\u03b1 and 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