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Lourdes Montserrat SIQUEIROS, Hugo Charles-Messance, Rodrigo Bolanos, Cecilia Montañez, José Sahel, Alvaro Rendon, Ramin Tadayoni, Audrey Giocanti; Role of Dexamethasone preventing Müller glial cells swelling. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4196.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal edema is due to vascular leakage and/or through cytotoxic events (e.g., glial cell swelling); Müller glial cells (MGC) play a crucial role regulating the volume of the extracellular space and water and ion homeostasis as well as preserving the blood retinal barrier.Erreur ! Référence de lien hypertexte non valide.We had previously showed that dystrophin Dp71 has a central role in the molecular scaffold responsible for anchoring AQP4 and Kir4.1 in MGC. HSF1 is a transcriptional regulator of Dp71.Dexamethasone (Dex) is a corticosteroid commonly used for the treatment of many retinal diseases (diabetic macular edema, vein occlusions), despite their exact mechanism remaining imperfectly understood.The purpose of this study was to analyze, on retinal explants, the effect of MGC swelling on Dp71 Kir4.1, AQP4, β-DG and ε-SG expression and to determine the role of Dex preventing the swelling and its effects.
According to the ARVO guidelines for animal use for research, 8 weeks WT mice retina were used in a retinal explant model to reproduce the effect of retinal edema on MGC, the retinas were incubated 8h in an hypotonic solution with Barium (Ba).The soma of MGC was measured using the software Image J. We quantified by qPCR Kir4.1, AQP4, β-DG, ε-SG, Dp71 and HSF1 expression.In the same conditions the retinas were treated at baseline with Dex and the same parameters were tested.
We observed an increase of MGC soma volume 8h after incubation in hypotonic solution with Ba associated with a decrease of Dp71 (34%), β-DG (23%), AQP4 (56%) and Kir4.1 (50%) mRNA expression comparing with control. ε-SG and HSF1 expression were not modified.When Dex was added to the retinal explants the MGC swelling was prevented and Dp71, β-DG, AQP4 and Kir4.1 expression were comparable to control retina. Moreover, in presence of Dex we observed an increase of HSF1 expression (84%).
Edema formation and resolution is a complex mechanism. Using retinal explants, we reproduced MGC swelling and observed an alteration of AQP4, Kir4.1 channels, in this model MGC swelling seems to be related with an inhibition on Dp71 expression. Moreover the addition of Dex to the retinal explants prevents this phenomenon and the results suggest it is related to an increase on HSF1 expression.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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