Compound 49b Restores Retinal Thickness and Reduces Degenerate Capillaries in the Rat Retina following Ischemia/Reperfusion.
Compound 49b Restores Retinal Thickness and Reduces Degenerate Capillaries in the Rat Retina following Ischemia/Reperfusion.
复制标题
DOI：
10.1371/journal.pone.0159532
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Steinle JJ
中科院分区：
文献类型：
--
作者：
Liu L;Jiang Y;Steinle JJ
我们最近报道说，一种新型的β-肾上腺素能受体激动剂的化合物可以显着降低在糖尿病样条件下生长的视网膜内皮细胞中的VEGF水平，我们研究了化合物49b是否可以在低氧下保护视网膜。在大鼠中使用缺血 - 重新灌注（I/R）诱导的模型的条件，以及在缺氧条件下培养的REC。在I/R时，在I/R后2天进行了对神经节细胞层的残留厚度和细胞损失的分析，而在I/R之后10天进行了脱水的毛细血管和周细胞幽灵在正常氧或缺氧（5％O2）中培养REC，或用50 nm化合物49b处理12小时后，将复合49B暴露后十二小时。 （IGFBP-3），血管内皮细胞生长因子（VEGF）及其受体（KDR），Angiopietin 1及其受体TIE2用于蛋白质印迹数据周围的幽灵49B治疗抑制了在缺氧中培养的残留变化，IGFBP-3水平降低了，这显着增加了化合物49b在49b处理后，这些数据降低了。
We have recently reported that Compound 49b, a novel β-adrenergic receptor agonist, can significantly reduce VEGF levels in retinal endothelial cells (REC) grown in diabetic-like conditions. In this study, we investigated whether Compound 49b could protect the retina under hypoxic conditions using the ischemia-reperfusion (I/R)-induced model in rats, as well REC cultured in hypoxic conditions. Some rats received 1mM topical Compound 49b for the 2 (5 rats each group) or 10 (4 rats in each group) days post-I/R. Analyses for retinal thickness and cell loss in the ganglion cell layer was done at 2 days post-I/R, while numbers of degenerate capillaries and pericyte ghosts were measured at 10 days post-I/R. Additionally, REC were cultured in normal oxygen or hypoxia (5% O2) only or treated with 50 nM Compound 49b for 12 hours. Twelve hours after Compound 49b exposure, cells were collected and analyzed for protein levels of insulin-like growth factor binding protein 3 (IGFBP-3), vascular endothelial cell growth factor (VEGF) and its receptor (KDR), angiopoietin 1 and its receptor Tie2 for Western blotting. Data indicate that exposure to I/R significantly decreased retinal thickness, with increasing numbers of degenerate capillaries and pericyte ghosts. Compound 49b treatment inhibited these retinal changes. In REC cultured in hypoxia, levels of IGFBP-3 were reduced, which were significantly increased by Compound 49b. Hypoxia significantly increased protein levels of VEGF, KDR, Angiopoiein 1, and Tie2, which were reduced following Compound 49b treatment. These data strongly suggested that Compound 49b protected the retina against I/R-induced injury. This provides additional support for a role of β-adrenergic receptor actions in the retina.