Zhang Jing Shang, Da Wang Jin, An Ying, Xiong Ying, Li Jing, Jonas JostB, Xu Liang, Zhang Wei, Wan Xiu Hua
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University; Beijing Key Laboratory of Ophthalmology & Visual Sciences, Beijing, China.
Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.
Mol Vis. 2017 Jun 16;23:346-355. eCollection 2017.
This study investigated the effect of cedilanid on retinal neovascularization in a mouse model of oxygen-induced retinopathy.
Seven-day-old C57BL/6 mice were exposed to 75% ± 1% oxygen for 5 days and were then returned to room air to induce retinal neovascularization. Cedilanid (0.025-0.2 μg) was intravitreally injected into the left eye of each mouse on postnatal day 12 (P12) and P15. PBS was intravitreally injected into the right eye as a control. Retinal neovascularization was evaluated with isolectin GS-IB4 staining of the retinal blood vessels. The function of reestablishment blood vessels was evaluated with angiography with the injection of fluorescein isothiocyanate (FITC)-dextran followed by isolectin GS-IB4 staining. Real time (RT)-PCR and western blot were used to examine the mRNA and protein expression of hypoxia inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF), respectively.
Retinal neovascular areas and obliterative areas were statistically significantly smaller in the eyes injected with cedilanid (0.05 μg, 0.1 μg, and 0.2 μg) compared with the control eyes. The inhibitory effect of cedilanid was observed in a dose-dependent manner. In addition, the retinal neovascular areas and the obliterative areas in the eyes injected with 0.2 μg cedilanid on P12 were statistically significantly smaller than those in the eyes injected with the same dose of cedilanid on P15. Cedilanid promoted the circulative function of reestablished blood vessels in the obliterative areas. Cedilanid inhibited the expression of HIF-1α and VEGF in mice treated with hyperoxia.
Cedilanid inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. Early treatment with cedilanid produces better inhibition of retinal neovascularization. Cedilanid may be a potential treatment of neovascular diseases.
本研究在氧诱导视网膜病变小鼠模型中研究西地兰对视网膜新生血管形成的影响。
7日龄C57BL/6小鼠暴露于75%±1%氧气中5天，然后放回室内空气中以诱导视网膜新生血管形成。在出生后第12天（P12）和第15天，将西地兰（0.025 - 0.2μg）玻璃体内注射到每只小鼠的左眼。将PBS玻璃体内注射到右眼作为对照。用视网膜血管的异凝集素GS-IB4染色评估视网膜新生血管形成。通过注射异硫氰酸荧光素（FITC）-葡聚糖后进行异凝集素GS-IB4染色的血管造影术评估重建血管的功能。分别使用实时（RT）-PCR和蛋白质印迹法检测缺氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）的mRNA和蛋白表达。
与对照眼相比，注射西地兰（0.05μg、0.1μg和0.2μg）的眼中视网膜新生血管区域和闭塞区域在统计学上显著更小。西地兰的抑制作用呈剂量依赖性。此外，在P12注射0.2μg西地兰的眼中视网膜新生血管区域和闭塞区域在统计学上显著小于在P15注射相同剂量西地兰的眼中。西地兰促进了闭塞区域重建血管的循环功能。西地兰抑制了高氧处理小鼠中HIF-1α和VEGF的表达。
西地兰在氧诱导视网膜病变小鼠模型中抑制视网膜新生血管形成。早期用西地兰治疗对视网膜新生血管形成的抑制效果更好。西地兰可能是一种治疗新生血管疾病的潜在药物。
