Department of Ophthalmology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France.
Centre de Recherche des Cordeliers, INSERM, Physiopathology of Ocular Diseases: Therapeutic Innovations, University Paris Cité, Paris, France.
Sci Rep. 2023 Aug 29;13(1):14111. doi: 10.1038/s41598-023-41126-0.
The exact link between systemic and ocular endogenous corticoids (steroidome) is unclear and whether the ocular steroidome is altered in CSCR eyes is unknown. The aims of this study were to analyze the human steroidome in the aqueous humor as a function of age, sex and time of the day, to correlate systemic and ocular steroidome and to analyze the ocular steroidome in long lasting complex inactive CSCR. Based on our results, we present two CSCR cases treated by the combination of oral mineralocorticoid antagonist and glucocorticoids drops. In a cross-sectional study, aqueous humor (AH) was collected between 8am and 6 pm from 50 unaffected individuals (25 men and 25 women) and from 14 patients with chronic CSCR, during cataract surgery. In addition, simultaneous serum and AH were collected from 27 individuals undergoing cataract surgery and, simultaneous AH and vitreous were collected from 9 patients undergoing cataract and vitrectomy to estimate corticoids levels in the different compartments. The steroidome was determined using a LC-MS/MS method that quantifies 13 endogenous corticoids from the gluco, mineralocorticoid and androgen pathways. In AH and vitreous, the highest corticoid level is reached by cortisol (F), that represents less than 10% of F serum level. The cortisol levels in the serum did not correlate with ocular cortisol levels. Serum and ocular cortisone (E) levels correlate, although less than 5% of circulating E reaches the eye. The only mineralocorticoids measured in the AH were corticosterone (B) and its inactive form, the 11-desoxycorticosterone (A). There was no influence of circadian rhythm on cortisol ocular levels and there was no correlation between the age or the sex and the level of F, E, A, and B. In eyes with chronic inactive CSCR, the levels of the active glucocorticoid form F was lower than in control eyes and the F/E ratio was reduced by 50% but the B/A ratio was higher indicating imbalance towards active mineralocorticoids. Base on this observation, we propose to combine an antagonist of the mineralocorticoid receptor together with topical glucocorticoids in two CSCR patients, resistant to all other treatments, with favorable outcome. Our results indicate that the ocular psteroidome is highly regulated suggesting a local metabolism of ocular corticoids. In eyes with long-lasting complex inactive CSCR, the steroidome analysis shows lower active glucocorticoids and higher active mineralocorticoids.
内源性系统性和眼内皮质激素（类固醇组）之间的确切联系尚不清楚，CSCR 眼内的眼内类固醇组是否发生改变也尚不清楚。本研究的目的是分析房水中的人体类固醇组作为年龄、性别和时间的函数，以关联系统性和眼内类固醇组，并分析长期持续的复杂非活动性 CSCR 中的眼内类固醇组。基于我们的结果，我们提出了两种 CSCR 病例，通过联合口服盐皮质激素拮抗剂和糖皮质激素滴注进行治疗。在一项横断面研究中，在白内障手术期间，于上午 8 点至下午 6 点从 50 名无影响个体（25 名男性和 25 名女性）和 14 名慢性 CSCR 患者中收集房水（AH）。此外，同时从 27 名接受白内障手术的个体中收集血清和 AH，并从 9 名接受白内障和玻璃体切除术的患者中同时收集 AH 和玻璃体，以估计不同隔室中的皮质激素水平。使用 LC-MS/MS 方法测定类固醇组，该方法定量测定来自葡糖、盐皮质激素和雄激素途径的 13 种内源性皮质激素。在 AH 和玻璃体中，皮质醇（F）达到最高皮质激素水平，F 仅占血清 F 水平的不到 10%。血清皮质醇水平与眼内皮质醇水平不相关。血清和眼内可的松（E）水平相关，尽管不到 5%的循环 E 到达眼睛。在 AH 中测量的唯一盐皮质激素是皮质酮（B）及其无活性形式 11-去氧皮质酮（A）。昼夜节律对皮质醇眼内水平没有影响，年龄或性别与 F、E、A 和 B 的水平之间没有相关性。在患有慢性非活动性 CSCR 的眼中，活性糖皮质激素形式 F 的水平低于对照眼中，F/E 比值降低了 50%，但 B/A 比值升高，表明向活性盐皮质激素的平衡发生了变化。基于这一观察结果，我们建议在两名对所有其他治疗均有抵抗力的 CSCR 患者中联合使用盐皮质激素受体拮抗剂和局部糖皮质激素治疗，结果良好。我们的结果表明，眼内 psteroidome 受到高度调节，表明眼内皮质激素的局部代谢。在长期持续的复杂非活动性 CSCR 眼中，类固醇组分析显示活性糖皮质激素较低，活性盐皮质激素较高。
