Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit MI, United States of America.
PLoS One. 2018 Sep 20;13(9):e0204346. doi: 10.1371/journal.pone.0204346. eCollection 2018.
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.
我们之前曾报道过，环磷酸腺苷交换蛋白 1（Epac1）可减少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潜在地导致视网膜损伤，我们假设 Epac1 会在暴露于缺血/再灌注（I/R）后保护视网膜免受神经元和血管损伤。为此，我们使用了 Epac1 基因敲除和内皮细胞特异性 Epac1 敲除小鼠。将它们暴露于缺血 90 分钟后再进行再灌注。在 I/R 后 1 天，一些小鼠用于荧光素血管造影成像或 Evan's 蓝通透性测量。在 I/R 后 2 天处死小鼠进行神经元测量，在 I/R 后 10 天进行退化毛细血管测量。数据显示，与接受相同治疗的 Epac1 floxed 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 还增加了所有视网膜层中 Epac1 EC-KO 小鼠退化毛细血管的数量和细胞丢失。与 Epac1 floxed 小鼠相比，I/R 后 Epac1 EC-KO 小鼠的视网膜厚度明显减少。综上所述，数据表明 Epac1 可防止暴露于 I/R 后视网膜的神经元和血管损伤。
