Conclusions
Our results suggest that potassium channels are critically involved in diabetes-induced gliosis and microglial activation. The KATP opener, pinacidil, can reduce microglial activation by upregulating Kir6.1 expression.
Methods
Primary and immortalized cell lines of retinal microglia and Müller cells were used to set up a coculture model. In the trans-well system, microglia were seeded in the upper chamber and Müller cells in the bottom chamber. Microglia were polarized into proinflammatory (M1, with lipopolysaccharide and INF-γ) with or without different pinacidil concentrations before coculturing with Müller cells. The expression of inflammatory or anti-inflammatory genes and protein in microglia, and the expression of glial fibrillary acidic protein (GFAP), Kir4.1, and AQP4 in Müller cells were examined by real-time polymerase chain reaction and Western blot. Pinacidil was injected intravitreally into streptozotocin-induced diabetic rats. Retinal gliosis and inflammation were examined by immunohistochemistry and Western blot.
Purpose
This study aimed to determine the effect of pinacidil, a nonselective KATP channel opener, on diabetes-induced retinal gliosis and inflammation.
Results
Intravitreal injection of pinacidil alleviated diabetes-induced Müller cell gliosis and microglial activation and reduced vascular endothelial growth factor expression. In vitro study demonstrated that pinacidil inhibited tumor necrosis factor and interleukin-1β expression in M1-type microglia and alleviated the M1 microglia-induced GFAP expression in the Müller cells. Furthermore, we found that pinacidil on its own, or in combination with IL-4, can upregulate arginase-1 (Arg-1) and Kir6.1 expression in microglial cells. Conclusions: Our results suggest that potassium channels are critically involved in diabetes-induced gliosis and microglial activation. The KATP opener, pinacidil, can reduce microglial activation by upregulating Kir6.1 expression.