title: Epithelial-Mesenchymal Transition (EMT)-Related Cytokines in the Aqueous Humor of Phakic and Pseudophakic Fuchs' Dystrophy Eyes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Mario
authors.initials: M
authors.lastname: Matthaei
authors.forename: Johannes
authors.initials: J
authors.lastname: Gillessen
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Muether
authors.forename: Robert
authors.initials: R
authors.lastname: Hoerster
authors.forename: Björn O
authors.initials: BO
authors.lastname: Bachmann
authors.forename: Arno
authors.initials: A
authors.lastname: Hueber
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
authors.forename: Ludwig M
authors.initials: LM
authors.lastname: Heindl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism*; D002386:Cataract / Q000150:complications / Q000378:metabolism*; D002387:Cataract Extraction; D018932:Chemokine CCL2 / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D053782:Transforming Growth Factor beta3; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D014409:Tumor Necrosis Factor-alpha