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Gian Marco Tosi, Marì Regoli, Annalisa Altera, Federico Galvagni, Cataldo Arcuri, Tommaso Bacci, Ines Elia, Giulia Realini, Maurizio Orlandini, Eugenio Bertelli; Heat Shock Protein 90 Involvement in the Development of Idiopathic Epiretinal Membranes. Invest. Ophthalmol. Vis. Sci. 2020;61(8):34. doi: https://doi.org/10.1167/iovs.61.8.34.
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This work was aimed to further characterize cells of idiopathic epiretinal membranes (iERMs). We wanted to determine the contribution of 90-kDa heat shock protein (HSP90) to sustain the transforming growth factor-β (TGF-β)-mediated signal transduction pathway in iERM.
Immunofluorescence and confocal microscopy were carried out on deplasticized sections from 36 epiretinal membranes processed for electron microscopy and on frozen sections from five additional samples with antibodies against α-smooth muscle actin (αSMA), vimentin, glial fibrillary acidic protein (GFAP), SMAD2, HSP90α, type-II TGF-β1 receptor (TβRII), type-I collagen, and type-IV collagen. In addition, Müller MIO-M1 cells were transfected with HSP90 and challenged with TGF-β1.
Double and triple labeling experiments showed that a variable number of TβRII+ cells were present in 94.1% of tested iERMs and they were mostly GFAP−/αSMA+/vimentin+/HSP90α+. In almost half of the cases these cells contained type-I collagen, suggesting their involvement in matrix deposition. HSP90 overexpressing MIO-M1 cells challenged with TGF-β1 showed increased levels of TβRII, SMAD2, SMAD3, and phosphor-SMAD2. Nuclear SMAD2 staining could be observed in HSP90α+ cells on frozen sections of iERMs.
Cells in iERMs that express TβRII are also HSP90α+ and show the antigenic profile of myofibroblast-like cells as they are GFAP−/αSMA+/vimentin+. HSP90α-overexpressing MIO-M1 cells challenged with TGF-β1 showed an increased activation of the SMAD pathway implying that HSP90α might play a role in sustaining the TGF-β1-induced fibrotic response of iERM cells.
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