Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy
Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy
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DOI：
10.1007/s11427-015-4860-1
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发表时间：
2015-06-01
影响因子：
9.1
通讯作者：
Chung, Sookja Kim
中科院分区：
文献类型：
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作者：
Liu Jin;Yeung, Patrick Ka Kit;Chung, Sookja Kim
糖尿病视网膜病变出现缺血，伴有神经元丢失、水肿、胶质细胞反应性和氧化应激。Epas由Epac1和Epac2组成，是cAMP介质，在维持内皮屏障和神经元功能方面发挥重要作用。为探讨Epacs在缺血性视网膜病变发病机制中的作用，对Epac1基因缺陷小鼠(Epac1(-/-))、Epac2基因缺陷小鼠(Epac2(-/-))及其野生型小鼠(Epac1(+/+)和Epac2(+/+))进行短暂大脑中动脉阻塞(TMCAO)。采用缺血2小时和再灌流22小时的方法造成视网膜缺血再灌注损伤。TMCAO后，不同基因型间对侧视网膜形态相似。同侧视网膜神经元丢失，视网膜水肿，水通道蛋白4(AQP4)、胶质纤维酸性蛋白(GFAP)、过氧化还蛋白6(Prx6)免疫反应增强。Epac2(-/-)组同侧视网膜神经节细胞层神经元丢失较多，视网膜增厚，AQP4、GFAP、Prx6免疫组织化学染色较Epac2(+/+)组强。然而，Epac1(-/-)同侧视网膜表现出与Epac1(+/+)小鼠相似的病理改变。我们的观察结果表明，Epac2缺乏导致了视网膜缺血/再灌注损伤后更严重的缺血性视网膜病变。
Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac1 and Epac2, are cAMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions. To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion (tMCAO) was performed on Epac1-deficient (Epac1(-/-)) mice, Epac2-deficient (Epac2(-/-)) mice, and their wild type counterparts (Epac1(+/+) and Epac2(+/+)). Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After tMCAO, the contralateral retinae displayed similar morphology between different genotypes. Neuronal loss, retinal edema and increase in immunoreactivity for aquaporin 4 (AQP4), glial fibrillary acidic protein (GFAP), peroxiredoxin 6 (Prx6) were observed in ipsilateral retinae. Epac2(-/-) ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2(+/+). However, Epac1(-/-) ipsilateral retinae displayed similar pathology as those in Epac1(+/+) mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury.