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Xun Xu; A deca-peptide inhibits retinal neovascularization by down-regulation of VEGF and up-regulation of PEDF in OIR mouse. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1952.
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© ARVO (1962-2015); The Authors (2016-present)
Neovascular retinopathies collectively comprise the most common cause of blindness and affect millions of people from infants to the elderly. Our previous study has demonstrated that a novel deca-peptide, TKII-10, effectively inhibits angiogenesis in chick chorioallantoic membrane and corneal neovascularization. The purpose of this study is to investigate the inhibitory efficacy and mechanism of TKII-10 on retinal neovascularization, in an effort to develop a small peptide for clinical application in neovascular retinopathies.
(1) In vitro, MTS asssy, cell migration assay with tranwell chamber, and tube formation assay on Matrigel were carried out to evaluate the inhibitory effect of TKII-10 on VEGF induced retinal endothelial cell proliferation, migration, and tube formation. Bevacizumab (Avastin) was set as positive control, and a scramble peptide, TKII-10S, was set as negative control. (2) The antiangiogenic effect of TKII-10 was further confirmed in retinal neovascularization in oxygen-induced retinopathy in vivo. (3) In oxygen-induced retinopathy model, real time PCR and western blot assays were used to explore the influence of TKII-10 on the mRNA and protein expression of VEGF and PEDF in mouse retina.
(1) TKII-10 inhibited VEGF-induced endothelial cell migration and tube formation dose-dependently. TKII-10 did no inhibit endothelial VEGF-induced cell proliferation. (2) In OIR assay, the TKII-10 group demonstrated obviously reduced nonperfused area, less neovascular tuft at the junction, and improved vessel dilation compared with the PBS group. There was a significant reduction in the number of vascular cell nuclei extending from the retinal surface into the vitreous in TKII-10 group compared with the PBS group (p<0.01). (3) In oxygen-induced retinopathy, intravitreous injection of TKII-10 resulted in down-regulation of VEGF mRNA and protein expression, concomitant up-regulation of PEDF mRNA and protein expression in the oxygen plus TKII-10 group compared with the oxygen plus PBS group (p<0.01).
TKII-10 potently inhibits VEGF-induced endothelial cell migration and tube formation in vitro while it is inactive in inhibiting endothelial cell proliferation. TKII-10 effectively inhibits pathological retinal neovascularization by down-regulation of VEGF mRNA and protein expression and concominent up-regulation of PEDF mRNA and protein.
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