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学科主题: 临床医学
题名:
Antiangiogenesis Effects of Endostatin in Retinal Neovascularization
作者: Bai, Yu-jing; Huang, Lv-zhen; Zhou, Ai-yi; Zhao, Min; Yu, Wen-zhen; Li, Xiao-xin
刊名: JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
发表日期: 2013-09-01
DOI: 10.1089/jop.2012.0225
卷: 29, 期:7, 页:619-626
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Ophthalmology ; Pharmacology & Pharmacy
研究领域[WOS]: Ophthalmology ; Pharmacology & Pharmacy
关键词[WOS]: ENDOTHELIAL GROWTH-FACTOR ; EPITHELIUM-DERIVED FACTOR ; INHIBITS CHOROIDAL NEOVASCULARIZATION ; RECOMBINANT HUMAN ENDOSTATIN ; MACULAR DEGENERATION ; OCULAR NEOVASCULARIZATION ; INTRAVITREAL INJECTION ; DOWN-REGULATION ; FACTOR THERAPY ; TUMOR-GROWTH
英文摘要:

Purpose: Pathological retinal angiogenesis is a major cause of vision loss. Endostatin is a natural antiangiogenesis antitumor protein that is widely used in cancer studies. In this study, we investigated the efficacy and potential mechanisms of endostatin for the prevention of retinal neovascularization both in vitro and in vivo.

Methods: Human umbilical vein endothelial cells (HUVECs) were used for the in vitro studies. HUVECs were incubated with endostatin or the vascular endothelial growth factor (VEGF) and endostatin for different time points. Cell proliferation, migration, cell cycling, and tube formation studies were carried out using a Cell Counting Kit-8 assay, a Transwell assay, flow cytometry, and a Matrigel assay, respectively. Enzyme-Linked Immunosorbent Assay (ELISA) was used to study VEGF and pigment epithelial-derived factor (PEDF) protein secretion from the HUVECs at different time points. A murine oxygen-induced retinopathy (OIR) model was used for the in vivo studies. Seven-day-old C57BL/6J pups (p7) were exposed to 75% oxygen for 5 days. On p12, the animals were returned to a normal atmosphere and were immediately injected intravitreously with 1.5 mu L of a 5 mg/mL endostatin solution. At p18, the mice were perfused with fluorescein-dextran-FITC, and their retinas were flat mounted to measure the nonperfused area. Retinal VEGF and PEDF levels were also measured by ELISA Kits in the OIR mice at p18.

Results: In vitro, endostatin inhibited HUVEC proliferation in a dose-dependent manner and also inhibited HUVEC proliferation in a VEGF-containing medium. Additionally, endostatin can inhibit migration, tube formation, and VEGF secretion in HUVECs, while also inducing apoptosis in HUVECs at several time points. These effects were statistically significant when compared to the control group (P < 0.05). In vivo, a single intravitreous injection of endostatin reduced the retinal nonperfused area from 30% in the control group to 23% in the treatment group (P < 0.0001). Intravitreous injection of endostatin reduced VEGF levels in retinas, while it increased PEDF levels.

Conclusions: Endostatin showed convincing inhibitory effects on angiogenesis both in vitro and in vivo. The inhibitory effects may be, at least partly, resulted from the restoration of the PEDF/VEGF ratio. These data suggest that endostatin could offer an innovative pharmaceutical strategy for the prevention of retinal neovascularization.

语种: 英语
所属项目编号: 2011CB510200 ; RDB2012-24
项目资助者: National Basic Research Program of China (973 Program) ; Peking University People&prime ; s Hospital Research and Development Fund
WOS记录号: WOS:000339268700003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67485
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Key Lab Vis Loss & Restorat, Minist Educ,Dept Ophthalmol, Beijing 100044, Peoples R China

Recommended Citation:
Bai, Yu-jing,Huang, Lv-zhen,Zhou, Ai-yi,et al. Antiangiogenesis Effects of Endostatin in Retinal Neovascularization[J]. JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS,2013,29(7):619-626.
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