Elevated Levels of Growth/Differentiation Factor-15 in the Aqueous Humor and Serum of Glaucoma Patients.

Rupalatha Maddala,Anja Osterwald,Shruthi Karnam,Iris Navarro,Sandra S. Stinnett,Christoph Ullmer,Leona T. Y. Ho,Robin R. Vann,Ponugoti V. Rao,Pratap Challa

doi:10.3390/jcm11030744

Rupalatha Maddala, Anja Osterwald + Show 8 more

Open Access

https://doi.org/10.3390/jcm11030744

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Abstract

Dysregulated levels of growth/differentiation factor-15 (GDF15), a divergent member of the transforming growth factor-beta super family, have been found to be associated with the pathology of various diseases. In this study, we evaluated the levels of GDF15 in aqueous humor (AH) and serum samples derived from primary open-angle glaucoma (POAG) and age- and gender-matched non-glaucoma (cataract) patients to assess the plausible association between GDF15 and POAG. GDF15 levels were determined using an enzyme-linked immunosorbent assay, and data analysis was performed using the Wilcoxon rank sum test, or the Kruskal–Wallis test and linear regression. GDF15 levels in the AH (n = 105) of POAG patients were significantly elevated (by 7.4-fold) compared to cataract patients (n = 117). Serum samples obtained from a subgroup of POAG patients (n = 41) also showed a significant increase in GDF15 levels (by 50%) compared to cataract patients. GDF15 levels were elevated in male, female, African American, and Caucasian POAG patients. This study reveals a significant and marked elevation of GDF15 levels in the AH of POAG patients compared to non-glaucoma cataract control patients. Although serum GDF15 levels were also elevated in POAG patients, the magnitude of difference was much smaller relative to that found in the AH.

Highlights

Glaucoma, a group of optic neuropathies, is the second leading cause of irreversible blindness worldwide
We aimed to investigate whether dysregulated aqueous humor (AH) and serum growth/differentiation factor-15 (GDF15) levels relate to primary-open angle glaucoma (POAG)
We initially compared the levels of GDF15 in AH and serum samples from the same cohort of POAG patients (n = 40 and 41, respectively) with age- and gender-matched controls

Summary

Introduction

A group of optic neuropathies, is the second leading cause of irreversible blindness worldwide. Among the various characterized types of glaucoma, primary-open angle glaucoma (POAG) accounts for more than 70% [1,2]. The etiology of POAG is poorly understood, elevated intraocular pressure (IOP) due to impaired aqueous humor (AH) drainage through the trabecular pathway has been identified as a major risk factor for POAG [3,4]. Though several IOP-lowering drugs are currently available, many of them do not possess adequate efficacy to control IOP in glaucoma patients, with several posing considerable adverse effects [3]. A better understanding of the etiology of ocular hypertension and impaired AH outflow through the trabecular pathway, which accounts for more than 80% of AH outflow in glaucoma patients, is necessary to enable the development of targeted and efficacious IOP-lowering drugs [4,6]

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