Yang Zijian, Huang Ping, Liu Xiaohong, Huang Shouyue, Deng Lianfu, Jin Zhe, Xu Shuo, Shen Xi, Luo Xunda, Zhong Yisheng
Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin Er Road, 200025, Shanghai, China.
Shanghai Institute of Traumatology and Orthopaedics, 197 Ruijin Er Road, 200025, Shanghai, China.
Sci Rep. 2015 Jun 11;5:11294. doi: 10.1038/srep11294.
Müller cells are principal glial cells in rat retina and have attracted much attention in glaucoma studies. However, it is not clear whether adenosine and adenosine receptor (AR) antagonists play any roles in the regulation of potassium channels in Müller cells and subsequently in the promotion of glutamine synthetase (GS) and L-Glutamate/L-Aspartate Transporter (GLAST) functions. We found that chronic ocular hypertension (COH) in rat down-regulated Müller cells Kir2.1, Kir4.1, TASK-1, GS and GLAST expressions and attenuated the peak of inward potassium current. Retinal ganglion cells (RGC) count was lower in the COH rats than that in the sham operation animals. Intravitreal injection of selective A2A AR antagonist SCH442416 up-regulated Müller cell Kir4.1, TASK-1, GS and GLAST expressions and enhanced inward potassium currents compared with those in the COH rats with vehicle control. Meanwhile, the RGC count was higher following intravitreal injection of SCH442416 in the COH rats than that after vehicle injection. The fact that PKA inhibitor H-89 blocked these SCH442416 effects suggested that the PKA signaling pathway was involved in the observed ocular responses following the intravitreal SCH442416 injection.
缪勒细胞是大鼠视网膜中的主要神经胶质细胞,在青光眼研究中备受关注。然而,尚不清楚腺苷和腺苷受体(AR)拮抗剂是否在缪勒细胞钾通道的调节中发挥作用,进而是否在促进谷氨酰胺合成酶(GS)和L-谷氨酸/L-天冬氨酸转运体(GLAST)功能方面发挥作用。我们发现,大鼠慢性高眼压(COH)下调了缪勒细胞Kir2.1、Kir4.1、TASK-1、GS和GLAST的表达,并减弱了内向钾电流峰值。COH大鼠的视网膜神经节细胞(RGC)数量低于假手术动物。与注射赋形剂对照的COH大鼠相比,玻璃体内注射选择性A2A AR拮抗剂SCH442416上调了缪勒细胞Kir4.1、TASK-1、GS和GLAST的表达,并增强了内向钾电流。同时,在COH大鼠中,玻璃体内注射SCH442416后的RGC数量高于注射赋形剂后的数量。PKA抑制剂H-89阻断了这些SCH442416的作用,这一事实表明PKA信号通路参与了玻璃体内注射SCH442416后观察到的眼部反应。