Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI.
Mol Vis. 2021 May 21;27:365-369. eCollection 2021.
To determine whether forskolin, a protein kinase A (PKA) agonist, eye drops could reduce neuronal and vascular damage after exposure to ischemia/reperfusion (I/R).
C57BL/6J mice were exposed to the I/R protocol. A group of mice were given forskolin eye drops (10 μM) daily. Two days after I/R, neuronal measurements were performed, while vascular measurements were performed at 10 days post-I/R. Western blotting was conducted to investigate whether forskolin could increase PKA levels and reduce the levels of inflammatory mediators.
Forskolin statistically significantly increased PKA levels, but not exchange protein activated by cAMP 1 (Epac1). The forskolin eye drops also reduced neuronal and vascular damage compared to I/R alone. Tumor necrosis factor alpha (TNF-α) and interleukin-1-β (IL-1β) levels were statistically significantly reduced after administration of forskolin eye drops compared to I/R alone.
Forskolin eye drops were protective against I/R. The findings offer a new therapeutic for local delivery.
确定蛋白激酶 A（PKA）激动剂forskolin 滴眼液是否可以减轻暴露于缺血/再灌注（I/R）后的神经元和血管损伤。
C57BL/6J 小鼠接受 I/R 方案。一组小鼠每日给予 forskolin 滴眼液（10 μM）。I/R 后 2 天进行神经元测量，I/R 后 10 天进行血管测量。进行 Western blot 以研究 forskolin 是否可以增加 PKA 水平并降低炎症介质水平。
与 I/R 单独处理相比，forskolin 滴眼液可统计学显著增加 PKA 水平，但不增加环磷酸腺苷（cAMP）1 激活的交换蛋白（Epac1）。与 I/R 单独处理相比，forskolin 滴眼液还可减轻神经元和血管损伤。与 I/R 单独处理相比，肿瘤坏死因子-α（TNF-α）和白细胞介素-1-β（IL-1β）水平在给予 forskolin 滴眼液后统计学显著降低。
forskolin 滴眼液对 I/R 具有保护作用。该发现为局部给药提供了新的治疗方法。
