Upregulation of TGF-?1 in experimental proliferative vitreoretinopathy is accompanied by epithelial to mesenchymal transition

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• 作者：Robert Hoerster (1)
  Philipp S. Muether (1)
  Sarah Vierkotten (1)
  Manuel M. Hermann (1)
  Bernd Kirchhof (1)
  Sascha Fauser (1)
  
• 关键词：Proliferative vitreoretinopathy ; Animal model ; TGF ; ? ; Epithelial to mesenchymal transition
• 刊名：Graefe's Archive for Clinical and Experimental Ophthalmology
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：252
• 期：1
• 页码：11-16
• 全文大小：612 KB
• 作者单位：Robert Hoerster (1)
  Philipp S. Muether (1)
  Sarah Vierkotten (1)
  Manuel M. Hermann (1)
  Bernd Kirchhof (1)
  Sascha Fauser (1)
  
  1. Center of Ophthalmology, University of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany
  
• ISSN：1435-702X

文摘

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-?) has been suggested to play an important role in this process, but the role of TGF-? isoforms is unknown. Methods In pigmented rabbits (n--4), PVR was induced by cryopexy and a full-thickness limbus-parallel incision. PVR was evaluated by indirect ophthalmoscopy. Concentrations of TGF-? 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--), 2 (n--), 3 (n--), 4 (n--). Vimentin and alpha SMA were expressed during PVR development. During PVR development, both TGF-?1 levels (AH: p--.001; vitreous: p--.002) and TGF-?2 levels increased (AH: p--.027; vitreous: p--.02), while TGF-?3 was not detected at any timepoint. The increase was more pronounced for TGF-?1 than for TGF- ?2 (AH: p--.002; vitreous: p--.0005), and only TGF-?1 correlated with the amount of PVR (p--.024, r--,723). Conclusions Development of PVR membranes was accompanied by a pronounced upregulation of TGF-?1, rather than TGF-?2. Therefore TGF-?1 could be a promising target for inhibition of PVR.