Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Inserm, From Physiopathology of Retinal Diseases to Clinical Advances, 75006 Paris, France.
Assistance Publique-Hôpitaux de Paris, Department of Ophthalmology, Ophtalmopôle, Hôpital Cochin, 75014 Paris, France.
Int J Mol Sci. 2022 Jan 24;23(3):1278. doi: 10.3390/ijms23031278.
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 ( (encoding , and ) and in the RPE/choroid (, , and , , and ). 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 / 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.
中心性浆液性脉络膜视网膜病变（CSCR）是一种影响视网膜色素上皮（RPE）和脉络膜的视网膜疾病。这是一种公认的糖皮质激素（GCs）的副作用，通过鼻内、关节内、口服和皮肤途径给药。然而，GCs 眼内给药后不会发生 CSCR，这表明下丘脑-垂体-肾上腺轴（HPA）制动可能在 CSCR 和 GS 之间的机制联系中发挥作用。本研究旨在探讨这一假说。为了诱导 HPA 制动，Lewis 大鼠每天接受一次全身注射地塞米松，共 5 天。对照组大鼠接受生理盐水注射。通过 Elisa 在基线和第 5 天测量血清和眼内液中的皮质酮基线水平，并在第 5 天测量血清和眼内液中的地塞米松水平。定量测量神经视网膜和 RPE/脉络膜中编码糖皮质激素受体（GR）、盐皮质激素受体（MR）和 11β 羟类固醇脱氢酶（HSD）酶 1 和 2 的基因表达。在视网膜（编码 、 和 ）和 RPE/脉络膜（、、、、和 ）中定量测定 MR 靶基因的表达。只有 10%的皮质酮血清浓度在眼内液中被测量。地塞米松全身治疗 5 天后，血清和眼内液中的皮质酮水平下降，反映了 HPA 轴制动。虽然 GR 和 MR 在视网膜中均下调，但无 MR/GR 失衡，而在 RPE/脉络膜中，MR/GR 和 / 比值均增加，表明 MR 途径激活。MR 靶基因在 RPE/脉络膜中上调，但不在视网膜中上调。反复注射生理盐水引起的心理应激也导致 HPA 轴制动，RPE/脉络膜中 MR 途径有激活趋势。HPA 轴制动导致 RPE/脉络膜中皮质激素受体表达失衡，MR 途径过度激活，这可能有利于 CSCR 的发生。
