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K(ATP) Opener Attenuates Diabetic-Induced Müller Gliosis and Inflammation by Modulating Kir6.1 in Microglia

PURPOSE: This study aimed to determine the effect of pinacidil, a nonselective K(ATP) channel opener, on diabetes-induced retinal gliosis and inflammation. METHODS: Primary and immortalized cell lines of retinal microglia and Müller cells were used to set up a coculture model. In the trans-well syst...

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Detalles Bibliográficos
Autores principales: Li, Hong, Chen, Donglong, Sun, Wei, Chen, Jiansu, Luo, Chang, Xu, Heping, Ma, Jacey Hongjie, Tang, Shibo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862730/
https://www.ncbi.nlm.nih.gov/pubmed/33523201
http://dx.doi.org/10.1167/iovs.62.2.3
Descripción
Sumario:PURPOSE: This study aimed to determine the effect of pinacidil, a nonselective K(ATP) channel opener, on diabetes-induced retinal gliosis and inflammation. 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. 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 K(ATP) opener, pinacidil, can reduce microglial activation by upregulating Kir6.1 expression.