Antiangiogenesis Effects of Endostatin in Retinal Neovascularization
| Autor: | Ai-Yi Zhou, Wenzhen Yu, Xiaoxin Li, Lvzhen Huang, Min Zhao, Yujing Bai |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Vascular Endothelial Growth Factor A
Angiogenesis Blotting Western Angiogenesis Inhibitors Apoptosis Enzyme-Linked Immunosorbent Assay Retinal Neovascularization Biology Umbilical vein Mice chemistry.chemical_compound PEDF Cell Movement In vivo Human Umbilical Vein Endothelial Cells Animals Humans Retinopathy of Prematurity Pharmacology (medical) Nerve Growth Factors Eye Proteins Serpins Cell Proliferation Pharmacology Tube formation Matrigel Dextrans Flow Cytometry Fluoresceins Endostatins Mice Inbred C57BL Oxygen Vascular endothelial growth factor Disease Models Animal Ophthalmology Animals Newborn chemistry Immunology cardiovascular system Cancer research Female Endostatin |
| Zdroj: | Journal of Ocular Pharmacology and Therapeutics. 29:619-626 |
| ISSN: | 1557-7732 1080-7683 |
| DOI: | 10.1089/jop.2012.0225 |
| Popis: | 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.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 μL 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.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 (P0.05). 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 (P0.0001). Intravitrous injection of endostatin reduced VEGF levels in retinas, while it increased PEDF levels.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. |
| Databáze: | OpenAIRE |
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