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Epac1 protects the retina against ischemia/reperfusion-induced neuronal and vascular damage.
PLOS ONE ( IF 2.9 ) Pub Date : 2018-09-20 , DOI: 10.1371/journal.pone.0204346 Li Liu 1 , Youde Jiang 1 , Jena J Steinle 1
PLOS ONE ( IF 2.9 ) Pub Date : 2018-09-20 , DOI: 10.1371/journal.pone.0204346 Li Liu 1 , Youde Jiang 1 , Jena J Steinle 1
Affiliation
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We had previously reported that exchange protein for cAMP 1 (Epac1) reduced inflammatory mediators in the retina of mice and in retinal endothelial cells (REC). Since ischemia can induce retinal damage potentially through activation of inflammatory cascades, we hypothesized that Epac1 would protect the retina against neuronal and vascular damage after exposure to ischemia/reperfusion (I/R). We used Epac1 floxed and endothelial cell specific Epac1 knockout mice for this work. We exposed them to ischemia for 90 minutes followed by reperfusion. One day after I/R, some mice were used for fluorescein angiography imaging or Evan's blue measurements of permeability. Mice were sacrificed at 2 days for neuronal measurements and at 10 days for measurements of degenerate capillaries. Data show increased leakage in the Epac1 Cre-Lox (Epac1 EC-KO) mice exposed to I/R when compared to Epac1 floxed mice with the same treatment. I/R also increased numbers of degenerate capillaries and cell loss in all retinal layers of Epac1 EC-KO mice. Retinal thickness was reduced more significantly in the Epac1 EC-KO mice compared to Epac1 floxed mice after I/R. Taken together, the data suggest that Epac1 is protective against both neuronal and vascular damage to the retina after exposure to I/R.
中文翻译：
Epac1保护视网膜免受缺血/再灌注引起的神经元和血管损伤。
我们以前曾报道过，将cAMP 1（Epac1）的交换蛋白减少了小鼠视网膜和视网膜内皮细胞（REC）中的炎症介质。由于缺血可能通过激活炎症级联反应而潜在地引起视网膜损伤，因此我们假设Epac1在暴露于缺血/再灌注（I / R）后可保护视网膜免受神经元和血管损伤。我们使用Epac1固定和内皮细胞特异的Epac1基因敲除小鼠进行这项工作。我们将其暴露于局部缺血90分钟，然后再灌注。I / R后一天，将一些小鼠用于荧光素血管造影成像或通透性的Evan's Blue测量。在第2天处死小鼠以进行神经元测量，并在第10天处死小鼠以测量退化的毛细血管。数据显示，与经过相同处理的Epac1肥胖小鼠相比，暴露于I / R的Epac1 Cre-Lox（Epac1 EC-KO）小鼠的渗漏增加。I / R还增加了Epac1 EC-KO小鼠所有视网膜层中退化的毛细血管数量和细胞损失。与I / R后的Epac1肥胖小鼠相比，Epac1 EC-KO小鼠的视网膜厚度降低更为明显。两者合计，数据表明，Epac1在暴露于I / R后对视网膜的神经元和血管损伤均具有保护作用。
更新日期：2018-09-21
中文翻译：
Epac1保护视网膜免受缺血/再灌注引起的神经元和血管损伤。
我们以前曾报道过，将cAMP 1（Epac1）的交换蛋白减少了小鼠视网膜和视网膜内皮细胞（REC）中的炎症介质。由于缺血可能通过激活炎症级联反应而潜在地引起视网膜损伤，因此我们假设Epac1在暴露于缺血/再灌注（I / R）后可保护视网膜免受神经元和血管损伤。我们使用Epac1固定和内皮细胞特异的Epac1基因敲除小鼠进行这项工作。我们将其暴露于局部缺血90分钟，然后再灌注。I / R后一天，将一些小鼠用于荧光素血管造影成像或通透性的Evan's Blue测量。在第2天处死小鼠以进行神经元测量，并在第10天处死小鼠以测量退化的毛细血管。数据显示，与经过相同处理的Epac1肥胖小鼠相比，暴露于I / R的Epac1 Cre-Lox（Epac1 EC-KO）小鼠的渗漏增加。I / R还增加了Epac1 EC-KO小鼠所有视网膜层中退化的毛细血管数量和细胞损失。与I / R后的Epac1肥胖小鼠相比，Epac1 EC-KO小鼠的视网膜厚度降低更为明显。两者合计，数据表明，Epac1在暴露于I / R后对视网膜的神经元和血管损伤均具有保护作用。
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