Abstract
Purpose :
Central serous chorioretinopathy (CSCR) is a rare ocular side-effect of glucocorticoids (GCs). But contrarily to the other GCs-induced side effects, the route of GCs administration influences the risk of CSCR. The nasal, articular, oral and dermal routes favor CSCR but not the high and sustained intraocular GCs. To evaluate potential involvement of the hypothalamic-pituitary-adrenal axis (HPA) brake, we studied the corticosterone ocular levels and the corticoid receptors balance after chronic systemic dexamethasone treatment in rats.
Methods :
Lewis rats were untreated (N=7) or received systemic injection of either dexamethasone (N=16) or saline (N=5) daily for 5 days. 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 level of Nr3c1, Nr3c2, 11-bhsd1 and 2 were measured in the neural retina, retinal pigment epithelium (RPE)/choroid and iris/ciliary body. The expression of mineralocorticoid-induced genes was evaluated in the neural retina: Enac-a, Kir4.1 and Aqp4 and in the RPE/choroid: Shroom 2, Ngal, Mmp9, Omg, Ptx3, Plaur and Fosl-1.
Results :
After dexamethasone injection, corticosterone level significantly dropped in serum (p<0.0001) and in ocular media (p<0.002). After saline injection, serum corticosterone also dropped. In the neural retina, the expression of Nr3c1 encoding GR was down-regulated after treatment with dexamethasone (p<0.01) or saline (p<0.001), which was also seen for Nr3c2 encoding MR (p<0.001) but the Nr3c2/Nr3c1 expression balance did not change significantly. In the RPE/choroid of dexamethasone treated rats, a significant increase in the Nr3c2/Nr3c1 (p<0.01) and 11β-hsd2/11β-hsd1 (p<0.05) ratio was measured showing hyperactivation of MR pathway. In the retina, Enac-a, Kir4.1, Aqp4 were down-regulated after dexamethasone treatment (p<0.05). In RPE/choroid, the expression of Plaur (p<0.01) and Fosl-1 (p<0.05) was increased and Omg was reduced (p<0.05) after dexamethasone treatment, in line with MR overactivation.
Conclusions :
The HPA axis brake resulting from systemic chronic dexamethasone causes a significant reduction of systemic and ocular corticosterone and an imbalance of corticoid receptors expression in the RPE/choroid towards overactivation of MR, which could favor the occurrence of CSCR.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.