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Elodie Bousquet, Min Zhao, Guillaume Leroux les Jardins, Yvonne De Kozak, Francine Behar Cohen; Mineralocorticoid Receptor in the Eye during Endotoxin Induced Uveitis: Pro or Anti-inflammatory Activity ?. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5496.
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In addition to their role in controlling water and salt homeostasis, recent work suggested that aldosterone and mineralocorticoid receptor (MR) are involved in inflammation in several tissues and cell types. We have recently shown that retinal cells expressed MR and 11-beta-HSD2 demonstrating their mineralo-sensitivity. To determine the role of MR activation in the inflamed eye, we have evaluated the effects of aldosterone and spironolactone in the endotoxin induced uveitis (EIU).
EIU was induced by a systemic injection of lipopolysaccharide (LPS) in Lewis rat. One intravitreous injection of aldosterone (2 to 200nM) or spironolactone (10µM) was performed at the time of LPS challenge. Twenty four hours later, EIU was evaluated using clinical scoring and cytokines/chemokines concentration in ocular fluid using multiplex analysis. The expression of glucocorticoid receptor (GR) and MR was measured by real time PCR in iris/ciliary body at different time points after LPS injection and 24 hours after aldosterone or spironolactone treatment.
Unexpectedly, when evaluated at 24 hours, spironolactone did not only reduce EIU clinical score, but it rather enhanced it. Aldosterone induced a significant and dose-dependent reduction of EIU score, together with a reduction of inflammatory cytokines (TNF-alpha, IFN-gamma, IL-6, MCP-1) in ocular fluid whereas spironolactone intravitreal injection increased them.Interestingly, as soon as 3 hours after LPS injection, a drastic down-regulation of MR in iris/ciliary body was observed, whilst GR expression was only down-regulated at 24 hours after LPS injection.At 24 hours, aldosterone partially restored both MR and GR expression in ocular tissues whereas spironolactone enhanced increased MR down-regulation and had no influence on GR expression.
MR activation in EIU exerts anti-inflammatory effects. We suggest that the early MR down regulation preceding ocular inflammation, followed by GR repression could intervene in the suppression of endogenous glucocorticoids anti-inflammatory activity. The unexpected anti inflammatory effect of aldosterone could be related to a partial restoration of GR/MR expression in ocular tissues.
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