Abstract

Pseudoexfoliation (PXF) is a unique form of glaucoma characterized by accumulation of exfoliative material in the eyes. Changes in tear profile in disease stages may give us insights into molecular mechanisms involved in causing glaucoma in the eye. All patients were categorized into three main categories; pseudoexfoliation (PXF), pseudoexfoliation glaucoma (PXG) and cataract, which served as control. Cytokines, transforming growth factor β1 (TGFβ1), matrix metalloproteases (MMPs) and fibronectin (FN1) were assessed with multiplex bead assay, enzyme-linked immunosorbent assay (ELISA), gelatin zymography, and immunohistochemistry (IHC) respectively in different ocular tissues such as tears, tenon's capsule, aqueous humor (AH) and serum samples of patients with PXF stages. We found that TGFβ1, MMP-9 and FN1 protein expression were upregulated in tears, tenon's capsule and AH samples in PXG compared to PXF, though the MMP-9 protein activity was downregulated in PXG compared with control or PXF. We have also found that in PXG tears sample the fold change of TGF-α (Transforming Growth Factor-α), MDC (Macrophage Derived Chemokine), IL-8 (Interleukin-8), VEGF (Vascular Endothelial Growth Factor) were significantly downregulated and the levels of GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), IP-10 (Interferon- γ produced protein-10) were significant upregulated. While in AH; IL-6 (Interleukin-6), IL-8, VEGF, IFN-a2 (Interferon- α2), GRO (Growth regulated alpha protein) levels were found lower and IL1a (Interleukin-1α) level was higher in PXG compared to PXF. And in serum; IFN-a2, Eotaxin, GM-CSF, Fractalkine, IL-10 (Interleukin-10), IL1Ra (Interleukin-1 receptor antagonist), IL-7 (Interleukin-7), IL-8, MIP1β (Macrophage Inflammatory Protein-1β), MCP-1 (Monocyte Chemoattractant Protein-1) levels were significantly upregulated and PDGF-AA (Platelet Derived Growth Factor-AA) level was downregulated in the patients with PXG compared to PXF. Altered expression of these molecules in tears may therefore be used as a signal for onset of glaucoma or for identifying eyes at risk of developing glaucoma in PXF.

Highlights

  • Pseudoexfoliation (PXF) syndrome is a unique age related fibrillopathy characterized by mass deposition of white dandruff like material in different parts of anterior segment of the eye [1]

  • We found that transforming growth factor β1 (TGFβ1), matrix metalloproteinases (MMPs)-9 and FN1 protein expression were upregulated in tears, tenon’s capsule and aqueous humor (AH) samples in pseudoexfoliation glaucoma (PXG) compared to PXF, though the MMP-9 protein activity was downregulated in PXG compared with control or PXF

  • We have found that in PXG tears sample the fold change of TGF-α (Transforming Growth Factor-α), MDC (Macrophage Derived Chemokine), IL-8 (Interleukin-8), VEGF (Vascular Endothelial Growth Factor) were significantly downregulated and the levels of GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), IP-10 (Interferon- γ produced protein-10) were significant upregulated

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Summary

Introduction

Pseudoexfoliation (PXF) syndrome is a unique age related fibrillopathy characterized by mass deposition of white dandruff like material in different parts of anterior segment of the eye [1]. We elucidated different clinical correlates characterizing the different stages of pseudoexfoliation syndrome (PXF) and pseudoexfoliation glaucoma (PXG) with definite differences in tears of patients with PXG versus other forms of primary glaucoma [1, 2]. Vascular phenomenons such as vasospasm, systemic hypertension, angiographic vascular perfusion defects and oxidative stress markers such as generation of reactive oxygen species (ROS) have been found to be increased which partly explain the high incidence of ischemic ocular and systemic events associated with endothelial dysfunction seen characteristically in PXF [2,3,4,5,6,7]. The molecular mechanisms regulating clinical findings and those that cause transition from one phenotype to the other remain unclear

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