June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
A deca-peptide inhibits retinal neovascularization by down-regulation of VEGF and up-regulation of PEDF in OIR mouse
Author Affiliations & Notes
  • Xun Xu
    Department of Ophthalmology, Shanghai First People's Hospital, Shanghai, China
  • Footnotes
    Commercial Relationships Xun Xu, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1952. doi:
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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)

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Abstract

Purpose: 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.

Methods: (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.

Results: (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).

Conclusions: 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.

Keywords: 700 retinal neovascularization  
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