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

Abstract

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.

Transforming Growth Factor Beta Switch in Aqueous Humor of Patients With Fuchs' Endothelial Corneal Dystrophy

“…Similar to Matthaei et al, 1 we observed a significant upregulation of MCP-1 in FECD psph compared with FECD ph (P < 0.05) and Control ph (P < 0.001; Fig.). In addition, we found MCP-1 to be significantly upregulated in Edema psph compared with FECD ph (P < 0.001) and Control ph (P < 0.001).…”

“…In addition, there was a significant difference in TGF-b2 concentration between both phakic groups (P < 0.05) and between both pseudophakic groups (P < 0.05), respectively, with a higher concentration in patients with FECD. This suggests that TGFb2 is in fact specific for FECD within each category of phakic or pseudophakic eyes.Transforming growth factor b3 was below and TGF-b1 was above the detection limit in the study of Matthaei et al 1 In our study, it was the reverse. Therefore, we cannot comment on the findings for TGF-b1, but we can give new information on TGFb3.…”

“…Unlike Matthaei et al, 1 we also included a group with pseudophakic non-FECD edematous corneas (Edema psph ), and our analysis involved nine molecules in AH: five of them related to EMT (MCP-1, TGF-b1, TGF-b2, TGF-b3, and TNF-a), and four related to inflammation (IL-8/chemokine [CXC motif] ligand [CXCL]8, IL-6, growth-regulated oncogene a [GROa]/CXCL1 and IFN-a2). We compared Control ph (n ¼ 21) with FECD ph (n ¼ 5), FECD psph (n ¼ 19), and Edema psph (n ¼ 8).…”

“…Matthaei et al 1 found a significantly elevated concentration of MCP-1, TGF-b1, and TGF-b2 in pseudophakic FECD eyes (FECD psph ) compared with cataract controls (which we will abbreviate as Control ph ) and phakic FECD eyes (FECD ph ), but they observed no differences between FECD ph and Control ph . They rightly concluded that there was no primary role for these aqueous cytokines in FECD pathogenesis, but that the upregulation of these EMT-associated proteins in FECD psph was probably secondary to cataract surgery.…”

Preoperative Aqueous Cytokine Levels are Associated With Endothelial Cell Loss After Descemet's Stripping Automated Endothelial Keratoplasty

“…In recent years, elevated levels of cytokines in the AqH have been reported to be associated with pathogenesis in various ocular diseases, such as FECD, 35 glaucoma, 17,18,36 ocular surface diseases, 37 and graft rejection. 38,39 We reported an elevation of inflammatory cytokines in eyes with bullous keratopathy.…”