VEGF as a Paracrine Regulator of Conventional Outflow Facility.
VEGF as a Paracrine Regulator of Conventional Outflow Facility.
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DOI：
10.1167/iovs.16-20779
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发表时间：
2017-03-01
影响因子：
4.4
通讯作者：
Overby DR
中科院分区：
文献类型：
--
作者：
Reina-Torres E;Wen JC;Liu KC;Li G;Sherwood JM;Chang JY;Challa P;Flügel-Koch CM;Stamer WD;Allingham RR;Overby DR
血管内皮生长因子（VEGF）调节微血管内皮细胞的渗透性，而施累姆氏管（SC）内皮细胞的渗透性影响传统的房水流出。我们假设VEGF信号调节流出设施。我们测量了用VEGF-A164 a、VEGF-A165 b、VEGF-D或VEGF受体2（VEGFR-2）抑制剂灌注的去核小鼠眼中的流出功能（C）。在静态培养或循环拉伸24小时后，我们通过ELISA监测人小梁网（TM）细胞的VEGF-A分泌。我们使用免疫荧光显微镜定位VEGF-A蛋白在TM的小鼠。VEGF-A164 a增加去核小鼠眼中的C。周期性拉伸增加人TM细胞的VEGF-A分泌，这对应于小鼠TM中的VEGF-A定位。使用抑制剂SU 5416或Ki 8751或无活性剪接变体VEGF-A165 b阻断VEGFR-2可降低C。VEGF-D增加C，这可以被Ki 8751阻断。血管内皮生长因子是一种旁分泌调节剂的传统外流设施，分泌的TM细胞在响应机械应力。VEGF可能在SC内皮水平通过VEGFR-2影响功能。TM中VEGF信号传导的中断可以解释为什么抗VEGF治疗与流出道功能降低和持续性高眼压相关。
Vascular endothelial growth factor (VEGF) regulates microvascular endothelial permeability, and the permeability of Schlemm's canal (SC) endothelium influences conventional aqueous humor outflow. We hypothesize that VEGF signaling regulates outflow facility. We measured outflow facility (C) in enucleated mouse eyes perfused with VEGF-A164a, VEGF-A165b, VEGF-D, or inhibitors to VEGF receptor 2 (VEGFR-2). We monitored VEGF-A secretion from human trabecular meshwork (TM) cells by ELISA after 24 hours of static culture or cyclic stretch. We used immunofluorescence microscopy to localize VEGF-A protein within the TM of mice. VEGF-A164a increased C in enucleated mouse eyes. Cyclic stretch increased VEGF-A secretion by human TM cells, which corresponded to VEGF-A localization in the TM of mice. Blockade of VEGFR-2 decreased C, using either of the inhibitors SU5416 or Ki8751 or the inactive splice variant VEGF-A165b. VEGF-D increased C, which could be blocked by Ki8751. VEGF is a paracrine regulator of conventional outflow facility that is secreted by TM cells in response to mechanical stress. VEGF affects facility via VEGFR-2 likely at the level of SC endothelium. Disruption of VEGF signaling in the TM may explain why anti-VEGF therapy is associated with decreased outflow facility and sustained ocular hypertension.