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Robert Hoerster, Philipp S Muether, Bernd Kirchhof, Sascha Fauser; TGF-beta receptor dependent proliferation of RPE and glial cells in human PVR membranes.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4236.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal pigment epithelial (RPE) cells, as well as retinal glial cells contribute to the formation of tractional membranes in proliferative vitreoretinopathy (PVR). Transforming growth factor (TGF) beta induces epithelial to mesenchymal transition (EMT) of RPE cells into contractile myofibroblasts. While TGF-beta receptor (R) subtype 2 is located on glial cells, the TGF-beta receptor status of RPE cells is unclear. Moreover the role of TGF-beta receptors in cell proliferation is unclear. We aimed to analyze TGF-beta R1 and R2 expression and proliferation of RPE and glial cells in human PVR membranes.
20 human PVR membranes were obtained during surgery for PVR tractional retinal detachment. All membranes were fixated in 4% formaldehyde for at least 72 hours and embedded in paraffin. Immunohistochemical analysis of cross-sections was performed with glial cell marker anti-GFAP (Abcam, Cambridge, UK), proliferation marker anti-KI-67, anti-TGF-beta R1 (Santa Cruz Biotechnology, Dallas, Texas, USA) and R2 (Abcam, Cambridge, UK). Areas positive for GFAP and TGF-beta R1 and R2 were quantified semi-quantitatively in % of the whole section. KI-67 positive cells were counted completely.
Elongated RPE cells were found loosely scattered within the PVR membrane, inside and outside of GFAP positive areas. Fibrous tissue showed areas positive and negative for GFAP. Cells were always double-positive for TGF-beta R1 and R2. TGF-beta R1 and R2 were found on both pigmented cells, as well as GFAP positive cells. The proportion of GFAP positive areas was 24±23 (0-66)%. Proportion of TGF-beta receptor positive cells was 52±30 (0-100)%. Proliferation of cells, as detected by KI-67 was located in areas positive for TGF-beta receptors in 94±12 (0-100)%.
TGF-beta R1 and R2 were likewise found on glial, as well as RPE cells. This indicates an influence of TGF-beta on both cell types. Proliferation in PVR seems to predominantly take place in areas positive for TGF-beta receptors. This emphasizes the role of TGF-beta in the proliferation of RPE and glial cell within the pathogenesis of PVR. Interplay of TGF-beta R1 and R2 with their ligands is thus a promising therapeutical target.
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