SEARCHCOHORTophthalmology, retina

cohort·ophthalmology, retina, endocrinology, cataract surgery, preclinical research·PMC10465571

Ocular steroidome in human eyes and in eyes with complex central serous chorioretinopathy (CSCR)

Scientific Reports · 8 authors, 4 centres

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TL;DR

Using LC-MS/MS, this cohort study profiled corticoids (the steroidome) in aqueous humor and vitreous of human control eyes and eyes with inactive CSCR. The central result is that local ocular corticoid metabolism is independent from systemic steroid levels, and eyes with inactive CSCR show an imbalance toward lower active glucocorticoids and higher active mineralocorticoids.

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This cohort study used a highly sensitive and specific LC-MS/MS method to quantify corticoids from the mineralocorticoid, glucocorticoid, and androgen pathways in aqueous humor and vitreous from human eyes. Controls were cataract surgery patients sampled at different times of day, enabling correlative analyses of serum and aqueous humor. The study found that local corticoid metabolism in the aqueous humor is independent from the systemic steroidome, and that ocular cortisol levels are not influenced by systemic cortisol levels including circadian variations. In eyes with long-lasting complex but inactive CSCR, an imbalance was observed toward lower active glucocorticoids and higher active mineralocorticoids. Limitations include the limited number of CSCR samples due to the rarity of the disease, measurement during inactive disease only (without subretinal fluid), and the quantification of total corticoids (bound and unbound). The authors suggest that topical glucocorticoids might be beneficial for these patients, but larger cohort studies are needed to confirm these preliminary results.

STUDY TYPE

cohort

SPECIALTY

ophthalmology

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ORIGINAL PAPER

PMC10465571

Ocular steroidome in human eyes and in eyes with complex central serous chorioretinopathy (CSCR)

Scientific Reports

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ABSTRACT

Abstract 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. Subject terms: Metabolism, Neurophysiology, Biomarkers, Diseases, Endocrinology, Medical research, Molecular medicine

CITATION EXPORT

Marta Zola, Elodie Bousquet, Jean-Louis Bourges et al.. Ocular steroidome in human eyes and in eyes with complex central serous chorioretinopathy (CSCR). Scientific Reports. (2023). https://doi.org/10.1038/s41598-023-41126-0

AUTHORS

8 · 4 CENTRES

Marta Zola, Elodie Bousquet, Jean-Louis Bourges, Fréderic Azan, Min Zhao, Thara Jaworski, Eric Pussard, Francine Behar-Cohen

1Department of Ophthalmology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
2Centre de Recherche des Cordeliers, INSERM, Physiopathology of Ocular Diseases: Therapeutic Innovations, University Paris Cité, Paris, France
3Department of Ophthalmology, Hôpital Foch, Suresnes, France
4Department of Genetic and Hormonology, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris-Saclay, Le Kremlin Bicêtre, France