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Audrey Giocanti Auregan, Lourdes Siqueiros-Marquez, Hugo Charles-Messance, Romain Bénard, Cecilia Montañez, José Alain sahel, Florian Sennlaub, Xavier Guilloneau, Bahram Bodaghi, Ramin Tadayoni, Alvaro Rendon; Differential effect of corticosteroids on Müller glial cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5393.
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© ARVO (1962-2015); The Authors (2016-present)
Dexamethasone (dex), Triamcinolone (TA) and Fluocinolone acetonide (FA) are corticosteroids used for the treatment of macular edema, however their exact mechanisms on ocular tissues remain imperfectly understood.As dystrophin Dp71 is a protein expressed in Müller glial cells (MGC), and its absence has been related to blood retinal barrier permeability, and retinal osmotic alterations, through delocalization and down-regulation of the AQP4 and Kir4.1 channels, that dystrophin may contribute to edema formation. The purpose of this study was to analyze the ex vivo effect of MGC swelling on Dp71, AQP4, and Kir4.1 and assess the role of dex, TA, and FA at different doses to prevent the swelling and its effects.
According to the ARVO guidelines for animal use for research, 8 weeks WT mouse retinas were used in a retinal explant model. To reproduce a MGC swelling, the retinas were incubated 8h in a hypoosmotic solution and Ba2+, as a potassium channel blocker. To assess the swelling of the cells, the soma of MGC was measured using Image J software after staining. We quantified by qPCR the changes in the expression of Kir4.1, AQP4, β-DG and Dp71 due to the swelling of MGC. In the same conditions the retinas were treated with dex, FA or TA at baseline to assess the preventive effect of the drugs.
We observed a swelling of MGC 8h after incubation in hypotonic solution and Ba2+ associated to a down-regulation of Dp71, β-DG, AQP4 and Kir4.1. High doses (1780 µM) of dex, TA and FA prevented MGC swelling. We found a differential effect of corticosteroids depending on the dose. FA had no significant effect on MGC swelling at a dose lower than 5ng but prevent the swelling over this dose. At low dose (0.012µM) none of the three corticoids prevented down-regulation of Kir4.1 and AQP4. At a higher dose (1780 µM), dex did not prevent the down-regulation of Dp71 nor Kir4.1, but prevented AQP4 down-regulation, when at the same dose FA, and TA prevented the down-regulation of Dp71 and Kir4.1, but had no effect on AQP4.
Edema formation and resolution is a complex mechanism. In this model, we showed a differential effect of the 3 corticosteroids usually used in the treatment of retinal edema. We highlighted that the effect of corticosteroids on MGC is also dose dependent. This work suggests that the already known relative anti-inflammatory effect of corticosteroids may probably be different in the retina.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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