Correlation of NUCB2/Nesfatin-1 with Cytokine Levels in Primary Open-Angle Glaucoma

Milena Pahlitzsch; Raphaela Fritsche-Guenther; Inga Pompös; Dominika Pohlmann; Anna-Karina B Maier; Sibylle Winterhalter; Carl Erb; Anne Rübsam

doi:10.2147/OPTH.S307379

Correlation of NUCB2/Nesfatin-1 with Cytokine Levels in Primary Open-Angle Glaucoma

Clin Ophthalmol. 2021 Jun 16:15:2505-2517. doi: 10.2147/OPTH.S307379. eCollection 2021.

Authors

Milena Pahlitzsch¹, Raphaela Fritsche-Guenther², Inga Pompös¹, Dominika Pohlmann¹, Anna-Karina B Maier¹, Sibylle Winterhalter¹, Carl Erb³, Anne Rübsam¹

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
² Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Metabolomics Platform, Berlin, Germany.
³ Eye clinic Wittenbergplatz, Berlin, Germany.

Abstract

Purpose: Nesfatin-1 is produced in various tissues of the body including the hypothalamus. Neuroprotective properties of the neuropeptide hormone Nesfatin-1 were recently described. The aim of the study was to analyze the molecule Nesfatin-1 as a possible biomarker in POAG with neuroprotective properties pointing out the retinal-hypothalamic axis as target site in POAG and to obtain a molecular signature of cytokines in POAG as neuroinflammatory processes are a key factor of glaucoma development.

Methods: In this study, n=35 patients with moderate and advanced POAG (mean age 65.0y, IOP 13.9±3.0mmHg) and n=35 healthy controls (mean age 51.6y, IOP 14.3±2.7mmHg) were included. Clinical parameters including IOP, cup to disc ratio (CDR), glaucoma medication and retinal nerve fiber layer thickness (RNFL) were recorded. Plasma was collected for NUCB2/nesfatin-1 measurement using a Nesfatin-1 ELISA and for detection of 13 inflammatory cytokines using a multiplex bead-based immunoassay (MagPix). Multiple linear regression analysis was performed to adjust for confounding factors.

Results: Sex-independent or sex-dependent variables showed no significant differences in the Nesfatin-1 level (p>0.05). As a trend, an increase in NUCB2/nesfatin-1 in male glaucoma patients was found. Increased concentrations of 11 cytokines (GM-CSF, Interferon-γ, Interleukin-1β, IL-2, 4, 5, 6, 7, 10, 12 and TNF-α) were detected in POAG. The female glaucoma patients demonstrated elevated cytokine concentrations compared to male patients. NUCB2/nesfatin-1 showed a significant correlation to IL-2 and IL-13 levels in POAG. Stepwise multiple regression analysis showed no difference in NUCB2/nesfatin-1 level between POAG and healthy controls after adjusting for sex and age (all p>0.05).

Conclusion: As a trend, male POAG patients showed increased plasma NUCB2/nesfatin-1 levels. We further found inflammation as contributing factor to the pathogenesis of glaucoma, with a greater inflammatory response in women.

Keywords: NUCB2/nesfatin-1; cytokines; molecular signature; primary open-angle glaucoma.

Grants and funding

We acknowledge Jennifer Kirwan from the Berlin Institute of Health (BIH) Metabolomics Platform for providing the MagPix Instrument and the possibility to perform the ELISA experiments. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.