Download ID number: S423100806M (王中峰)

ID number: S423100806M (王中峰)
mGluR I-mediated inhibition of Kir channels contributes to
retinal Müller cell gliosis in a rat chronic ocular hypertension
model
1,2,4
Min Ji
, Yanying Miao
1,2,4
Sun
1,3,4
, Zhongfeng Wang
1
1,3,4
, Ling-Dan Dong
1,3,4
, Jie Chen
1,2,4
, Xiao-Fen Mo
, Xing-Huai
1,3,4,*
2
3
Institutes of Brain Science and Eye & ENT Hospital, Institute of Neurobiology
4
and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China
* Corresponding author. E-mail: [email protected]
Abstract Müller cell gliosis is a universal response in many retinal pathological
conditions, including glaucoma. Accompanying the enhanced expression of glial
+
fibrillary acidic protein (GFAP), the Kir K channel is downregulated in most, if
not all, retinal diseases. The mechanisms underlying Müller cell gliosis and the
+
downregulation of K currents are poorly understood. Here, we show that Müller cell
Kir currents were reduced significantly and GFAP expression was increased in a rat
chronic ocular hypertension (COH) model. The group I mGluR agonist DHPG mimicked
the COH-induced suppression of Kir currents, and this was selectively blocked by
2+
the mGluR5 antagonist MPEP. The intracellular Ca -dependent PLC/IP3-ryanodine/PKC
signaling pathway mediated the DHPG effect. COH-induced changes in Müller cells were
eliminated by injecting MPEP and were mimicked by an intravitreal injection of DHPG.
Thus, mGluR5-mediated suppression of Kir currents contributed to retinal Müller cell
gliosis in a rat COH model.
Key words: mGluR I; retinal Müller cell gliosis; Kir K+ channel; chronic ocular
hypertension