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Lourdes SIQUEIROS, Audrey Giocanti, Romain Benard, Ophelie Vacca, Cecilia Montañez, Jose Alain Sahel, Alvaro Rendon, Ramin Tadayoni; Role of inflammation and effect of Dexamethasone on Müller Glial Cells in a post-surgical model of blood-retinal barrier breakdown. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):159.
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Inner blood-retinal barrier (iBRB) breakdown is involved in macular edema formation. Alterations of Müller glial cells (MGC) under pathological conditions may contribute also to edema formation. One of the functions of MGC is the fluid absorption from retinal tissue, which is mediated by water (AQP4) and potassium (Kir4.1) membrane channels. Dystrophin Dp71, a cytoskeleton membrane associated protein, is responsible of the proper clustering and polarized expression of Kir4.1 and AQP4 in MGC. The absence of this protein leads to the iBRB breakdown.<br /> The purpose of this study was to analyze the effect of a post-surgical iBRB breakdown on Dp71 expression, to study the role of inflammation in this model and the effect of an intravitreal Dexamethasone (Dex) injection.
We produced a post-surgical iBRB breakdown model in mice by performing a partial lens surgery. We verified the iBRB breakdown by Evans Blue method after partial lens surgery. We quantified by qPCR and by Western Blot the expression of Kir4.1, AQP4, and Dp71, 72h after partial lens surgery. We also quantified the inflammatory biomarkers expression (ICAM-1, TNFα, VEGF-A) in the retina after partial lens surgery. Furthermore, in the same conditions we injected a single dose of Dex one day after partial lens surgery and evaluated the expression of AQP4, Kir4.1 and Dp71.
We observed that the BRB breakdown, 24 and 48 hours after partial lens surgery, was followed by a down-regulation of AQP4 and Dp71 by 30%, and a mislocalization of Kir4.1. Furthermore, we observed an increase of VEGF-A after surgery, but no increase of ICAM-1 or TNFα. When the surgery was followed by an intravitreal injection of Dex, despite of iBRB breakdown, expression of AQP4/Dp71 and localization of Kir4.1 were completely similar to control in which the iBRB was unbroken.
Blood-retinal breakdown is a complex mechanism, which involves MGC dysfunction. In this model, we showed that VEGF-A is involved but not the TNFα pathway. Dex, which is known to act on inflammatory processes, appears in our experimental model to play also a key role on MGC function preservation by the maintenance of the expression and membrane localization of Dp71 as well as AQP4 and Kir4.1 channels.
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