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Lourdes Siqueiros-Marquez, Romain Bénard, Ophélie Vacca, Hugo Charles-Messance, Rodrigo Bolaños-Jimenez, Xavier Guilloneau, Florian Sennlaub, Cecilia Montañez, José Alain Sahel, Alvaro Rendon, Ramin Tadayoni, Audrey Giocanti-Aurégan; Protection of Glial Müller Cells by Dexamethasone in a Mouse Model of Surgically Induced Blood–Retinal Barrier Breakdown. Invest. Ophthalmol. Vis. Sci. 2017;58(2):876-886. doi: 10.1167/iovs.16-20617.
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Breakdown of the inner blood–retinal barrier (iBRB) occurs in many retinal disorders and may cause retinal edema often responsible for vision loss. Dexamethasone is used in clinical practice to restore iBRB. The aim of this study was to characterize the impact of a surgically induced iBRB breakdown on retinal homeostatic changes due to dystrophin Dp71, aquaporin-4 (AQP4), and Kir4.1 alterations in Müller glial cells (MGC) in a mouse model. The protective effect of dexamethasone was assessed in this model. Moreover, retinal explants were used to control MGC exposure to a hypoosmotic solution containing barium.
Partial lens surgery was performed in C57BL6/J mice. Dystrophin Dp71, AQP4, and Kir4.1 expression was analyzed by quantitative RT-PCR, Western blot, and immunohistochemistry. Twenty-four hours after surgery, mice received a single intravitreal injection of dexamethasone or of vehicle.
After partial lens surgery, iBRB permeability increased while Dp71 and AQP4 were downregulated and Kir4.1 was delocalized. These effects were partially prevented by dexamethasone injection. In the retinal explant model, MGC were swollen and Dp71, AQP4, and Kir4.1 were downregulated after exposure to a hypoosmotic solution containing barium, but not in the presence of dexamethasone. Heat shock factor protein 1 (HSF1) was overexpressed in dexamethasone-treated retinas.
Partial lens surgery induces iBRB breakdown and molecular changes in MGC, including a downregulation of Dp71 and AQP4 and the delocalization of Kir4.1. Dexamethasone seems to protect retina from these molecular changes by upregulating HSF1.
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