title: Upregulation of TGF-ß1 in experimental proliferative vitreoretinopathy is accompanied by epithelial to mesenchymal transition.
abstract: BACKGROUND
  Proliferative vitreoretinopathy (PVR) is characterized by epithelial to mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells and consecutive formation of fibrous membranes, leading to retinal redetachment. Transforming growth factor beta (TGF-ß) has been suggested to play an important role in this process, but the role of TGF-ß isoforms is unknown.
  
  
  METHODS
  In pigmented rabbits (n = 14), PVR was induced by cryopexy and a full-thickness limbus-parallel incision. PVR was evaluated by indirect ophthalmoscopy. Concentrations of TGF-ß isoforms were determined by multiplex bead assay analysis in aqueous humor (AH) and vitreous samples. EMT marker vimentin was analyzed by western blot. Masson's-trichrome, haematoxilin and eosine (H&E), and immunohistochemical analysis for EMT marker alpha SMA were performed on cross-sections of eyes.
  
  
  RESULTS
  PVR was induced in all treated eyes. The number of quadrants affected by PVR was 1 (n = 5), 2 (n = 2), 3 (n = 2), 4 (n = 5). Vimentin and alpha SMA were expressed during PVR development. During PVR development, both TGF-ß1 levels (AH: p = 0.001; vitreous: p = 0.002) and TGF-ß2 levels increased (AH: p = 0.027; vitreous: p = 0.02), while TGF-ß3 was not detected at any timepoint. The increase was more pronounced for TGF-ß1 than for TGF- ß2 (AH: p = 0.002; vitreous: p = 0.0005), and only TGF-ß1 correlated with the amount of PVR (p = 0.024, r = 0,723).
  
  
  CONCLUSIONS
  Development of PVR membranes was accompanied by a pronounced upregulation of TGF-ß1, rather than TGF-ß2. Therefore TGF-ß1 could be a promising target for inhibition of PVR.
authors.affiliation: Center of Ophthalmology, University of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany, robert.hoerster@uk-koeln.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Hoerster
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Muether
authors.forename: Sarah
authors.initials: S
authors.lastname: Vierkotten
authors.forename: Manuel M
authors.initials: MM
authors.lastname: Hermann
authors.forename: Bernd
authors.initials: B
authors.lastname: Kirchhof
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D007124:Immunoenzyme Techniques; D011817:Rabbits; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism* / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D014746:Vimentin