Zhu Xiaowei, Lin Xuming, Xu Ying, Li Naiyang, Zhou Qing, Sun Xiaowei, Li Yuanbin
Department of Ophthalmology, Zhongshan City People's Hospital, Zhongshan, Guangdong, China.
Department of Ophthalmology, First Affiliated Hospital of Medical College of Jinan University, Guangzhou, Guangdong, China.
J Ophthalmol. 2021 Nov 19;2021:5688300. doi: 10.1155/2021/5688300. eCollection 2021.
Clinical studies have found that increasing levels of plasma endothelin-1 (ET-1) might inhibit choroidal blood flow (BF) and promote choroidal vasoconstriction. This study was designed to investigate ET-1 levels and its effect on choroidal microvascular morphology in a retinitis pigmentosa (RP) animal model.
Mice with retinal degeneration (rd10) were intragastrically administered bosentan, a dual endothelin receptor antagonist. We detected plasma ET-1 levels using an enzyme-linked immunosorbent assay (ELISA) kit at P14, P21, and P28 and evaluated ET-1 expression in RPE/choroid/sclera complexes using western blot and whole mount immunofluorescence staining at P28. Retinal thickness was measured using hematoxylin and eosin (H&E) staining at P28. At the same time, we also estimated choroidal microvascular densities using vascular luminal casting with a scanning electron microscope (SEM).
Plasma ET-1 levels were increased significantly in rd10 mice at P21 (65.48 ± 24.83 pg/ml) and P28 (85.89 ± 20.23 pg/ml) compared with C57BL/6J mice at P21 (33.52 ± 16.33 pg/ml) and P28 (42.38 ± 17.53 pg/ml); the expression of ET-1 was also upregulated in RPE/choroid/sclera complexes at P28. Bosentan inhibited ET-1 expression in plasma ( < 0.05) and RPE/choroid/sclera complexes at P28 in rd10 mice. Choroidal microvascular densities were decreased in rd10 mice, and bosentan could weaken these changes.
Plasma and local ET-1 was elevated in an animal model of RP, suggesting that it likely participates in the pathological progression of retinal degeneration and may thus provide a new intervention target. ET-1 blockade might exert its protective effect by elevating choroidal microvascular density via inhibition of ET-1.
临床研究发现，血浆内皮素 -1（ET-1）水平升高可能会抑制脉络膜血流（BF）并促进脉络膜血管收缩。本研究旨在调查视网膜色素变性（RP）动物模型中ET-1水平及其对脉络膜微血管形态的影响。
给视网膜变性（rd10）小鼠灌胃双重内皮素受体拮抗剂波生坦。在第14天、第21天和第28天使用酶联免疫吸附测定（ELISA）试剂盒检测血浆ET-1水平，并在第28天使用蛋白质印迹法和全层免疫荧光染色评估RPE/脉络膜/巩膜复合体中ET-1的表达。在第28天使用苏木精和伊红（H&E）染色测量视网膜厚度。同时，我们还使用扫描电子显微镜（SEM）通过血管腔铸型估计脉络膜微血管密度。
与C57BL/6J小鼠在第21天（33.52±16.33 pg/ml）和第28天（42.38±17.53 pg/ml）相比，rd10小鼠在第21天（65.48±24.83 pg/ml）和第28天（85.89±20.23 pg/ml）血浆ET-1水平显著升高；在第28天，RPE/脉络膜/巩膜复合体中ET-1的表达也上调。波生坦在第28天抑制了rd10小鼠血浆（<0.05）和RPE/脉络膜/巩膜复合体中ET-1的表达。rd10小鼠脉络膜微血管密度降低，波生坦可减弱这些变化。
RP动物模型中血浆和局部ET-1升高，表明其可能参与视网膜变性的病理进展，因此可能提供一个新的干预靶点。ET-1阻断可能通过抑制ET-1升高脉络膜微血管密度发挥其保护作用。
