Chronic Systemic Dexamethasone Regulates the Mineralocorticoid/Glucocorticoid Pathways Balance in Rat Ocular Tissues

Abstract

Central serous chorioretinopathy (CSCR) is a retinal disease affecting the retinal pigment epithelium (RPE) and the choroid. This is a recognized side-effect of glucocorticoids (GCs), administered through nasal, articular, oral and dermal routes. However, CSCR does not occur after intraocular GCs administration, suggesting that a hypothalamic-pituitary-adrenal axis (HPA) brake could play a role in the mechanistic link between CSCR and GS. The aim of this study was to explore this hypothesis. To induce HPA brake, Lewis rats received a systemic injection of dexamethasone daily for five days. Control rats received saline injections. Baseline levels of corticosterone were measured by Elisa at baseline and at 5 days in the serum and the ocular media and dexamethasone levels were measured at 5 days in the serum and ocular media. The expression of genes encoding glucocorticoid receptor (GR), mineralocorticoid receptors (MR), and the 11 beta hydroxysteroid dehydrogenase (HSD) enzymes 1 and 2 were quantified in the neural retina and in RPE/ choroid. The expression of MR target genes was quantified in the retina (Scnn1A (encoding ENac-α, Kir4.1 and Aqp4) and in the RPE/choroid (Shroom 2, Ngal, Mmp9 and Omg, Ptx3, Plaur and Fosl-1). Only 10% of the corticosterone serum concentration was measured in the ocular media. Corticosterone levels in the serum and in the ocular media dropped after 5 days of dexamethasone systemic treatment, reflecting HPA axis brake. Whilst both GR and MR were downregulated in the retina without MR/GR imbalance, in the RPE/choroid, both MR/GR and 11β-hsd2/11β-hsd1 ratio increased, indicating MR pathway activation. MR-target genes were upregulated in the RPE/ choroid but not in the retina. The psychological stress induced by the repeated injection of saline also induced HPA axis brake with a trend towards MR pathway activation in RPE/ choroid. HPA axis brake causes an imbalance of corticoid receptors expression in the RPE/choroid towards overactivation of MR pathway, which could favor the occurrence of CSCR.

Bioinformatics Analysis of Immune Cell Infiltration and Diagnostic Biomarkers between Ankylosing Spondylitis and Inflammatory Bowel Disease

“…PLAUR is a crucial gene in chronic pruritus and functions through E1-PLAUR signaling [ 61 ]. Besides, one animal study showed that PLAUR played negative feedback regulation of glucocorticoid pathways in rats' ocular tissues [ 62 ]. Some scholars have found that PLAUR facilitated paclitaxel resistance and endometrial cancer cell invasiveness [ 63 ].…”

Author Response: Relationship of Choroidal Vasculature and Choriocapillaris Flow With Alterations of Salivary α-Amylase Patterns in Central Serous Chorioretinopathy

“…We are interested in reading the in vitro study cited by Menean et al 1 concerning the implications of the differential expression of receptors for glucocorticoid hormones in rat ocular tissues in an experimental model of hypothalamic–pituitary–adrenocortical axis downregulation. 18 However, from the currently available literature, we do not believe it is possible to establish or even exclude a link between salivary α-AMY changes and glucocorticoid receptors (both mineralocorticoid and glucocorticoid receptor) in humans with acute/chronic CSC. 2 , 15 – 17 , 19 , 20 …”

Pathomechanisms in central serous chorioretinopathy: A recent update

“…A curious phenomenon is the relative lack of CSCR development following intraocular corticosteroid injections. Zola et al hypothesized that the hypothalamic-pituitary-adrenal axis is inhibited by intraocular corticosteroids [45]. To test their hypothesis, rats were injected with intraocular dexamethasone daily for five days, and levels of corticosterone in ocular media were measured on day five.…”