Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility.
Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility.
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DOI：
10.1371/journal.pone.0161332
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tanihara H
中科院分区：
文献类型：
--
作者：
Fujimoto T;Inoue T;Maki K;Inoue-Mochita M;Tanihara H
抗血管内皮生长因子（VEGF）抗体治疗是眼血管生成的有效治疗方法。虽然抗VEGF治疗后一些患者的眼内压升高，但VEGF-A对房水流出途径的影响仍不清楚。本研究探讨了VEGF-A对眼房水流出通路的影响。我们使用人重组VEGF 121和VEGF 165。从食蟹猴的眼睛中分离小梁网（TM）和施莱姆氏管内皮（SCE）细胞。通过RT-PCR检测编码四种VEGF受体VEGFR 1（FLT 1）、VEGFR 2（KDR）、神经纤毛蛋白-1和神经纤毛蛋白-2的mRNA的表达。为了评估细胞单层的渗透性，我们测量了跨内皮电阻（TEER）。在用30 ng/mL VEGF 121处理48 h的灌注猪眼前节器官培养物中测量流出设施。TM和SCE细胞中表达4种VEGF-A相关受体mRNA。TM细胞的TEER不受VEGF 121或VEGF 165处理的显著影响。相比之下，30 ng/mL VEGF 121处理后48 h SCE细胞的TEER显著降低至基线的69.4 ± 12.2%（n = 10），与对照组相比有显著差异（P = 0.0001）。VEGF 165（30 ng/mL）处理后48 h SCE细胞TEER较基线（n = 10）下降72.3 ± 14.1%，与对照组相比差异无统计学意义（P = 0.0935）。选择性VEGFR 2抑制剂Ki 8751可完全抑制VEGF 121对SCE细胞通透性的影响，而选择性VEGFR 1抑制剂ZM 306416对VEGF 121诱导的TEER降低无影响。与对照组相比，30 ng/mL VEGF 121灌注48 h显著增加了流出功能（47.8 ± 28.5%，n = 5，P = 0.013）。这些结果表明，VEGF-A可能通过VEGFR 2调节SCE细胞的常规水流出。
Anti-vascular endothelial growth factor (VEGF) antibody therapy is an effective treatment for ocular angiogenesis. Although the intraocular pressure of some patients increases after anti-VEGF therapy, the effects of VEGF-A on the aqueous humor outflow pathway remain unknown. This study investigated the effects of VEGF-A on the aqueous humor outflow pathway. We used human recombinant VEGF121 and VEGF165. Trabecular meshwork (TM) and Schlemm’s canal endothelial (SCE) cells were isolated from the eyes of cynomolgus monkeys. Expression of mRNA coding four VEGF receptors, VEGFR1 (FLT1), VEGFR2 (KDR), neuropilin-1, and neuropilin-2, was examined by RT-PCR. To evaluate the permeability of cell monolayers, we measured transendothelial electrical resistance (TEER). The outflow facility was measured in perfused porcine anterior segment organ cultures treated with 30 ng/mL VEGF121 for 48 h. Four VEGF-A-related receptor mRNAs were expressed in TM and SCE cells. The TEER of TM cells was not significantly affected by VEGF121 or VEGF165 treatment. In contrast, the TEER of SCE cells was significantly lower 48 h after treatment with 30 ng/mL VEGF121 to 69.4 ± 12.2% of baseline (n = 10), which was a significant difference compared with the control (P = 0.0001). VEGF165 (30 ng/mL) decreased the TEER of SCE cells at 48 h after treatment to 72.3 ± 14.1% compared with the baseline (n = 10), which was not a significant difference compared with the control (P = 0.0935). Ki8751, a selective VEGFR2 inhibitor, completely suppressed the effect of VEGF121 on SCE cell permeability, although ZM306416, a selective VEGFR1 inhibitor, did not affect the VEGF121-induced decrease in TEER. Perfusion with 30 ng/mL of VEGF121 for 48 h significantly increased the outflow facility compared with the control (47.8 ± 28.5%, n = 5, P = 0.013). These results suggest that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2.
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