Epithelial-Mesenchymal Transition (EMT)-Related Cytokines in the Aqueous Humor of Phakic and Pseudophakic Fuchs' Dystrophy Eyes.

Abstract

The present study aimed to analyze the expression of epithelial-mesenchymal transition (EMT)-related cytokines in the aqueous humor of phakic and pseudophakic Fuchs' endothelial corneal dystrophy (FECD) eyes and their correlation to FECD severity. Aqueous humor samples from phakic FECD eyes (FECDph, n = 9), from pseudophakic FECD eyes more than 1 year after cataract surgery (FECDpsph, n = 13), and from cataract controls without FECD (Controlcat, n = 28) were obtained during Descemet membrane endothelial keratoplasty (DMEK) or cataract surgery. Expression of EMT-related cytokines (TGF-β1, TGF-β2, TGF-β3, MCP-1, BFGF, TNF-α, IL-1β) was measured using multiplex bead assay. Corneal central-to-peripheral thickness ratio at 3.5 mm from the center (CPTR3.5) was determined as an objective metric for FECD severity before surgery by slit-scanning pachymetry. Pseudophakic FECD eyes showed significantly elevated expression compared with Controlcat and FECDph eyes for TGF-β1 (P < 0.001, respectively), for TGF-β2 (P < 0.05, respectively), and MCP-1 (P < 0.001, respectively). Levels of TGF-β1 (r = 0.6116, P < 0.05) and MCP-1 (r = 0.5934, P < 0.05) were positively correlated with CPTR3.5. No differences in EMT-associated protein levels were detected comparing FECDph eyes and Controlcat eyes. Simultaneous elevation of TGF-β1, TGF-β2, and MCP-1 concentrations in FECDpsph eyes confirms that cataract surgery leads to long-term alterations of the intraocular microenvironment. Positive correlation of increased aqueous TGF-β1 and MCP-1 levels with CPTR3.5 in pseudophakic FECD eyes suggests that changed cytokine levels may be involved in corneal decompensation after cataract surgery. Unchanged aqueous humor levels of EMT-related proteins analyzed in phakic FECD patients indicate that there is no primary role of these aqueous cytokines in FECD pathogenesis.