Endocan Blockade Suppresses Experimental Ocular Neovascularization in Mice
| Autor: | Yanji Zhu, Yiyun Yao, Anna M. Demetriades, Yisheng Zhong, Ting Su, Ailing Sui, Yushuo Gao, Jikui Shen, Xi Shen, Bing Xie |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Angiogenesis Blotting Western Mice Transgenic Retinal Neovascularization Real-Time Polymerase Chain Reaction 03 medical and health sciences chemistry.chemical_compound Mice medicine Animals Fluorescent Antibody Technique Indirect Tube formation business.industry Endothelial Cells Retinal Vessels Retinal Antibodies Neutralizing eye diseases Choroidal Neovascularization Recombinant Proteins Neoplasm Proteins Blot Vascular endothelial growth factor Endothelial stem cell Mice Inbred C57BL Vascular endothelial growth factor A Disease Models Animal 030104 developmental biology Choroidal neovascularization chemistry Gene Expression Regulation Intravitreal Injections Cancer research Proteoglycans sense organs medicine.symptom business |
| Zdroj: | Investigative ophthalmologyvisual science. 59(2) |
| ISSN: | 1552-5783 |
| Popis: | Purpose Ocular neovascularization (NV) is a pathologic process characterized by the proliferation and infiltration of various types of cells such as RPE, glial, and endothelial cells, which interact with proangiogenic factors and inflammatory cytokines. Endocan is known to be enriched in retinal endothelial tip cells under hypoxia, but the effect of endocan on ocular NV progression is largely unknown. In this study, we investigated the role of endocan in the ocular NV pathologic process and the possible mechanisms involved. Methods In the eyes of mice with oxygen-induced retinopathy (OIR); choroidal NV (CNV); and rhodopsin promoter (rho)/VEGF transgenic mice, endocan expression was assessed by quantitative real-time PCR (RT-PCR) and Western blot. In vivo, a specific functional antibody was used to neutralize endocan and ocular NV levels were evaluated by RT-PCR, Western blot and immunostaining of flat-mounts. In vitro, the effect of endocan on human retinal microvascular endothelial cell (HREC) tube formation was observed using a routine method. Results Endocan was significantly elevated in these three experimental mice models. Endocan blockade with the neutralizer intravitreal injection not only suppressed the area of retinal, choroidal and subretinal NV, but also resulted in a decrease in several angiogenesis-associated molecules. Recombinant endocan protein (rhEndocan) was found to induce tube formation on HRECs directly. Conclusions The current data suggest that endocan is a potential therapeutic or an additional target for retinal and subretinal NV diseases. |
| Databáze: | OpenAIRE |
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