Elevated levels of GDF-15 in both the Aqueous Humor and Serum of Primary Open-Angle Glaucoma Patients

Abstract

Purpose : Growth/differentiation factor 15 (GDF-15), which belongs to the TGF-beta superfamily of growth factors, is recognized as an all-cause mortality/stress marker and prognostic protein of various diseases. GDF-15 also serves as a key regulator of various cellular pathways. Having detected the presence of GDF-15 in human and mouse aqueous humor (AH) samples and secretion of GDF-15 by trabecular meshwork (TM) cells, in this study we evaluated the levels of GDF-15 in both AH and serum samples obtained from primary open-angle glaucoma patients.

Methods : AH and blood samples were collected following informed consent from glaucoma and cataract patients who underwent surgery at the Duke Eye Center. Serum samples and cell/tissue debris free AH samples were analyzed for GDF-15 content by ELISA. Data were compared between age and gender matched glaucoma and cataract patients.

Results : GDF-15 levels in AH (n=50) and serum (n=54) samples derived from the same patients were significantly elevated in POAG patients (P<0.001; Wilcoxon rank sum test of difference between medians equal to zero) by ~10-fold and 79%, respectively, compared to samples from cataract patients (n=33-39). Moreover, analysis of a larger set (n=117) of AH samples from POAG patients also showed a significant (P<0.001; by ~9 fold) elevation in the levels of GDF-15 relative to AH from cataract patients (n=113). GDF-15 levels were elevated in both male and female glaucoma patients, with no apparent gender differences. Similarly, both African American and Caucasian glaucoma patients exhibited elevated levels of GDF-15 with no significant racial differences.

Conclusions : In support of a previous report, this large sample size study not only reveals significantly elevated levels of GDF-15 in the AH but also in the serum of POAG patients compared to non-glaucoma patients. These findings indicate that serum GDF-15 levels might serve as a biomarker for the diagnosis of POAG. Additionally, the robustly elevated levels of GDF-15 detected in the AH of glaucoma patients warrants studies to investigate the role of GDF-15 in the pathobiology of ocular hypertension and glaucoma.

This is a 2021 ARVO Annual Meeting abstract.