1. Phosphomannopentaose sulfate (PI-88) suppresses angiogenesis by downregulating heparanase and vascular endothelial growth factor in an oxygen-induced retinal neovascularization animal model
- Author
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Xian-Jun, Liang, Ling, Yuan, Jie, Hu, Hong-Hua, Yu, Tao, Li, Shao-Fen, Lin, and Shi-Bo, Tang
- Subjects
Vascular Endothelial Growth Factor A ,Infant, Newborn ,Down-Regulation ,Oligosaccharides ,Retinal Neovascularization ,eye diseases ,Mice, Inbred C57BL ,Oxygen ,Disease Models, Animal ,Mice ,Animals, Newborn ,Animals ,Humans ,Retinopathy of Prematurity ,sense organs ,Injections, Intraperitoneal ,Glucuronidase ,Research Article - Abstract
Purpose Vascular endothelial growth factor (VEGF) is the most potent angiogenic mitogen, and has been associated with angiogenesis. Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains, which can induce VEGF expression. The aims of the present study were to evaluate the heparanase expression and its relationship with VEGF in the retina of oxygen-induced retinopathy (OIR) mice, and to investigate the effect of the heparanase inhibitor phosphomannopentaose sulfate (PI-88) in the OIR retinas. Methods Seventy-seven newborn C57BL/6 mice were involved in this study. On postnatal day 7 (P7), pups were exposed to a hyperoxia condition (75% oxygen) for 5 days, and on P12, the mice were returned to room air. Control mice were exposed to room air from birth until P17, with normally developing retinal vasculature. PI-88 was administered intraperitoneally to OIR mice at a dose of 35.7 mg/kg/day for 5 consecutive days. The expression level of heparanase and VEGF in the retinas was assayed using immunohistochemistry, Q-RT–PCR, and western blot. Results The expression levels of heparanase and VEGF were increased in the OIR retinas compared with the control mice. The Q-RT–PCR results showed that the mRNA expression levels of heparanase and VEGF in OIR retina were increased 1.71 fold (p
- Published
- 2011