Endocan Blockade Suppresses Experimental Ocular Neovascularization in Mice
Endocan Blockade Suppresses Experimental Ocular Neovascularization in Mice
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Endocan 阻断抑制小鼠实验性眼部新生血管形成
DOI：
10.1167/iovs.17-22945
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发表时间：
2018
影响因子：
4.4
通讯作者：
Xie Bing
中科院分区：
文献类型：
--
作者：
Su Ting;Zhong Yisheng;Sui Ailing;Yao Yiyun;Gao Yushuo;Zhu Yanji;Demetriades Anna M.;Shen Jikui;Shen Xi;Xie Bing
目的：眼新生血管形成（NV）是一种病理过程，其特征在于各种类型的细胞如RPE、神经胶质细胞和内皮细胞的增殖和浸润，这些细胞与促血管生成因子和炎性细胞因子相互作用。已知内皮聚糖在缺氧条件下在视网膜内皮尖端细胞中富集，但内皮聚糖对眼部NV进展的影响在很大程度上是未知的。在这项研究中，我们调查的作用，内皮素在眼部NV的病理过程和可能的机制involved.Methods：在小鼠的眼睛与氧诱导的视网膜病变（OIR）;脉络膜NV（CNV）;和视紫红质启动子（rho）/VEGF转基因小鼠，内皮素的表达进行了评估，通过定量实时PCR（RT-PCR）和蛋白质印迹。在体内，使用特异性功能性抗体中和内皮聚糖，并通过RT-PCR、Western印迹和平板免疫染色来评估眼部NV水平。结果：在体外培养的人视网膜微血管内皮细胞（human retinal microvascular endothelial cell，HREC）模型中，Endocan的表达明显升高，与对照组相比，差异有统计学意义（P < 0. 05）。玻璃体内注射中和剂阻断内皮聚糖不仅抑制了视网膜、脉络膜和视网膜下NV的面积，而且还导致了几种血管生成相关分子的减少。重组内皮蛋白（rhEndocan）被发现直接诱导HRECs.Conclusions管形成：目前的数据表明，endocan是一个潜在的治疗或视网膜和视网膜下NV疾病的额外目标。
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.