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Jingwen Ding, Ningli Wang; Ischemic Preconditioning Induces Delayed Ischemic Tolerance Against Retinal Ischemia/Reperfusion Injury Via MEK/ERK Pathway. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1388.
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Ischemic preconditioning (IPC) of the retina can provide potent protection against ischemia/reperfusion injury, suggesting that the stimulation of endogenous protective processes in the retina could be used to treat ischemic retinal diseases. Although the molecular mechanism of IPC in the retina is not fully understood, our studies have led us to hypothesize that the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in retinal glial cells plays a crucial role.
Retinal ischemia was induced in rats by elevating intraocular pressure. Subcellular fractionation, Western blotting and immunostaining techniques were used to determine the phosphorylation and translocation status of ERK1/2 after retinal IPC. Recovery from ischemia performed 24 h after IPC was assessed histologically at 7 d following ischemia, with or without inhibition of the MEK/ERK pathway. Changes in retinal glial reaction were also evaluated using glial fibrillary acidic protein (GFAP) immunostaining.
Expression of phosphorylated ERK1/2 increased significantly with IPC, beginning at 20 min and persisting before 12 h. The signal was predominantly expressed in the end-feet of Müller glial cell. IPC dramatically decreased the thinning of outer and inner retinal layers and the loss of neuronal cell bodies that normally attend ischemia. Specific inhibition of ERK1/2 activation with U0126 prior to IPC blocked its neuroprotective effect and downregulated GFAP expression in Müller glial cells.
Our results indicate that activation of the MEK/ERK pathway and stimulation of a Müller glial cell reponse, contribute to the protective effects of IPC in the retina.
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