Vasoactivity of retinal veins: A potential involvement of endothelin-1 (ET-1) in the pathogenesis of retinal vein occlusion (RVO)
Vasoactivity of retinal veins: A potential involvement of endothelin-1 (ET-1) in the pathogenesis of retinal vein occlusion (RVO)
复制标题
DOI：
10.1016/j.exer.2018.07.016
复制
发表时间：
2018-11-01
影响因子：
3.4
通讯作者：
Ikeda, Tsunehiko
中科院分区：
文献类型：
--
作者：
Kida, Teruyo;Flammer, Josef;Ikeda, Tsunehiko
目的：虽然视网膜静脉阻塞（RVO）的发病机制尚不清楚，但全身性高血压和内皮素-1（ET-1）水平升高是已知的危险因素。因此，我们研究了ET-1对高血压大鼠视网膜静脉的影响。方法：我们关注自发性高血压大鼠(SHR)视网膜静脉的行为。为了确定 ET-1 是否与 SHR 眼中的血流相关，在全身麻醉下静脉注射 ET-1 之前和之后，使用激光散斑血流成像仪（LSFG-Micro，Softcare，福冈，日本）评估大鼠脉络膜视网膜血流。此外，摘除 SHR 和年龄匹配的正常血压 Wistar-Kyoto 大鼠 (WKY) 的视网膜，并对视网膜切片进行 ET-A 和 ET-B 受体的免疫染色。通过蛋白质印迹分析测定视网膜组织中ET-1受体和缺氧诱导因子1（HIF-1）的蛋白水平。结果：注射ET-1后，SHR的视网膜中的一根视网膜静脉变得异常收缩并几乎闭塞，并且视网膜脉络膜血流显着减少。 SHR 视网膜对 ET-A 受体的免疫反应性高于 WKY 视网膜。 SHR 视网膜中 ET-A 受体和 HIF1 的蛋白水平也显着高于 WKY 视网膜。结论：循环血液中 ET-1 的增加导致视网膜静脉局部收缩，并且这种效应在高血压大鼠中通过 ET-A 受体的上调而加剧。这种视网膜静脉收缩可能会增加视网膜静脉压，甚至可能导致 RVO 的发病机制。
Purpose: Whilst the pathogenesis of retinal vein occlusion (RVO) is still unclear, systemic hypertension and increased level of endothelin-1 (ET-1) are known risk factors. Therefore, we studied the influence of ET-1 on the retinal veins in hypertensive rats.Methods: We focused on the behavior of retinal veins in spontaneous hypertensive rats (SHR). To determine whether ET-1 was associated with the blood flow in eyes of SHRs, the chorioretinal blood flow in the rats was assessed using laser speckle flowgraphy (LSFG-Micro, Softcare, Fukuoka, Japan) before and after an intravenous injection of ET-1 under general anesthesia. In addition, retinas from SHRs and age-matched normotensive Wistar-Kyoto rats (WKYs) were removed, and retinal sections were immunostained for the ET-A and ET-B receptors. The protein levels of both ET-1 receptors and hypoxia-inducible factor 1 (HIF-1) in the retinal tissues were also determined by western blot analysis.Results: One of the retinal veins became exceptionally constricted and was nearly occluded, and the chorioretinal blood flow significantly decreased in the retinas of SHRs following the injection of ET-1. Immunoreactivity to ET-A receptor was higher in SHR retinas than in WKY retinas. The protein levels of ET-A receptor and HIF1 were also significantly higher in SHR retinas than in WKY retinas.Conclusions: An increase of ET-1 in circulating blood leads to the local constriction of retinal veins and this effect is accentuated in hypertensive rats by an upregulation of ET-A receptor. It is plausible that such a constriction of retinal veins increases retinal venous pressure, and may even contribute to the pathogenesis of RVO.