Suppression of choroidal neovascularization by Endostar in rats

Liu,Jian; Ye,Panpan; Su,Zhaoan; Lin,Kana; He,Fengying; Xu,Wen

doi:10.3892/mmr.2014.3132

May-2015 Volume 11 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

May-2015 Volume 11 Issue 5

Full Size Image

Article

Suppression of choroidal neovascularization by Endostar in rats

Authors:
- Jian Liu
- Panpan Ye
- Zhaoan Su
- Kana Lin
- Fengying He
- Wen Xu
View Affiliations / Copyright

Affiliations: Eye Center, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
Pages: 3621-3625
|
Published online on: December 23, 2014

https://doi.org/10.3892/mmr.2014.3132
Expand metrics +

Abstract

Choroidal neovascularization (CNV) is common in various retinal and choroidal diseases, and may result in severe and irreversible loss of vision. Our previous studies suggested that Endostar, a novel recombinant endostatin, is able to inhibit the proliferation and migration of choroid‑retinal endothelial cells. To further evaluate the effect of Endostar on the formation of CNV in vivo, a rat model of laser‑induced CNV was constructed and Endostar or phosphate‑buffered saline treatment was administered intravitreally every other day. Using fluorescein angiography (FA), reduced CNV incidence and leakage grade was observed in the Endostar group. In addition, CNV area and maximal thickness were prominently reduced in the Endostar group measured by choroid flat mounts and sections. Furthermore, vascular endothelial growth factor (VEGF), hypoxia‑inducible factor 1α and chemokine C‑X‑C motif ligand 1 were markedly reduced in the Endostar group as determined by quantitative polymerase chain reaction and downregulation of VEGF was also verified by western blot analysis at the protein level. This study demonstrates that Endostar suppressed CNV in a rat model, which may be largely mediated by the downregulation of VEGF and other angiogenic molecules.

View Figures

View References

1	Grossniklaus HE and Green WR: Choroidal neovascularization. Am J Ophthalmol. 137:496–503. 2004. View Article : Google Scholar : PubMed/NCBI
2	Yu MJ, Shen WY, Lai MC, Constable IJ, Papadimitriou JM and Rakoczy PE: The role of vascular endothelial growth factor (VEGF) in abnormal vascular changes in the adult rat eye. Growth Factors. 17:301–312. 2000. View Article : Google Scholar : PubMed/NCBI
3	Kwak N, Okamoto N, Wood JM and Campochiaro PA: VEGF is major stimulator in model of choroidal neovascularization. Invest Ophthalmol Vis Sci. 41:3158–3164. 2000.PubMed/NCBI
4	Rosenfeld PJ, Brown DM, Heier JS, et al: Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 355:1419–1431. 2006. View Article : Google Scholar : PubMed/NCBI
5	Ling Y, Yang Y, Lu N, et al: Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF -induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells. Biochem Biophys Res Commun. 361:79–84. 2007. View Article : Google Scholar : PubMed/NCBI
6	Song HF, Liu XW, Zhang HN, et al: Pharmacokinetics of His-tag recombinant human endostatin in Rhesus monkeys. Acta Pharmacol Sin. 26:124–128. 2005. View Article : Google Scholar : PubMed/NCBI
7	Ma X, Yao Y, Yuan D, et al: Recombinant human endostatin endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice. PLoS One. 7:e534492012. View Article : Google Scholar
8	Marneros AG, She H, Zambarakji H, et al: Endogenous endostatin inhibits choroidal neovascularization. FASEB J. 21:3809–3818. 2007. View Article : Google Scholar : PubMed/NCBI
9	Mori K, Ando A, Gehlbach P, et al: Inhibition of choroidal neovascularization by intravenous injection of adenoviral vectors expressing secretable endostatin. Am J Pathol. 159:313–320. 2001. View Article : Google Scholar : PubMed/NCBI
10	Kim C, Yu HG and Sohn J: The anti-angiogenic effect of chlorogenic acid on choroidal neovascularization. Korean J Ophthalmol. 24:163–168. 2010. View Article : Google Scholar : PubMed/NCBI
11	Honda M, Asai T, Umemoto T, Araki Y, Oku N and Tanaka M: Suppression of choroidal neovascularization by intravitreal injection of liposomal SU5416. Arch Ophthalmol. 129:317–321. 2011. View Article : Google Scholar : PubMed/NCBI
12	Sudhakar A, Sugimoto H, Yang C, Lively J, Zeisberg M and Kalluri R: Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins. Proc Natl Acad Sci USA. 100:4766–4771. 2003. View Article : Google Scholar : PubMed/NCBI
13	Nyberg P, Heikkilä P, Sorsa T, et al: Endostatin inhibits human tongue carcinoma cell invasion and intravasation and blocks the activation of matrix metalloprotease-2, -9, and -13. J Biol Chem. 278:22404–22411. 2003. View Article : Google Scholar : PubMed/NCBI
14	Rehn M, Veikkola T, Kukk-Valdre E, et al: Interaction of endostatin with integrins implicated in angiogenesis. Proc Natl Acad Sci USA. 98:1024–1029. 2001. View Article : Google Scholar : PubMed/NCBI
15	Abdollahi A, Hahnfeldt P, Maercker C, et al: Endostatin’s antiangiogenic signaling network. Mol Cell. 13:649–663. 2004. View Article : Google Scholar : PubMed/NCBI
16	Jia H and Kling J: China offers alternative gateway for experimental drugs. Nat Biotechnol. 24:117–118. 2006. View Article : Google Scholar : PubMed/NCBI
17	Zhao ZZ, Cao Y, Liu ZS, et al: Effects of recombinant human endostatin on peritoneal angiogenesis in peritoneal dialysis rats. Nephrology (Carlton). 16:599–606. 2011. View Article : Google Scholar
18	Lin M, Hu Y, Chen Y, et al: Impacts of hypoxia-inducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization. Invest Ophthalmol Vis Sci. 53:6197–6206. 2012. View Article : Google Scholar : PubMed/NCBI
19	Zhou J, Pham L, Zhang N, et al: Neutrophils promote experimental choroidal neovascularization. Mol Vis. 11:414–424. 2005.PubMed/NCBI
20	Strieter RM, Polverini PJ, Kunkel SL, et al: The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 270:27348–27357. 1995. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Suppression of choroidal neovascularization by Endostar in rats

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles