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Robert Hoerster, Philipp S. Muether, Bernd Kirchhof, Sascha Fauser; Upregulation Of TGF-ß1 In Experimental Proliferative Vitreoretinopathy Is Accompanied By Epithelial To Mesenchymal Transition. Invest. Ophthalmol. Vis. Sci. 2012;53(14):891.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative vitreoretinopathy (PVR) is characterized by the formation of fibrous membranes, leading to retinal redetachments after vitreoretinal surgery. Retinal pigment epithelium cells (RPE cells) are key players in the pathogenesis of PVR. They undergo epithelial to mesenchymal transition (EMT) to form myofibroblasts expressing vimentin as an intracellular protein. The isoforms 1 and 2 of transforming growth factor beta (TGF-ß) promote fibrosis via induction of EMT. TGF-ß3 inhibits fibrosis. To estimate the role of TGF-ß isoforms in the pathogenesis of PVR we analysed TGF-ß1, 2 and 3 during the course of experimental PVR.
Female, pigmented rabbits (chinchilla bastard) were treated with 180° circumferential retinal cryopexy, followed by a 6mm full-thickness incision 3mm posterior to the limbus. Wound treatment was conducted using biodegradable sutures. Animals were examined for 28 days (d) using indirect ophthalmoscopy. Anterior chamber (AC) and vitreous samples were obtained at d0 and at d28. After sacrification on d28 the eyes were removed and flatmounted for PVR grading. Complete retinal and choroidal tissue-samples were obtained for detection of vimentin by western blot. TGF-ß isoform concentrations were determined by multiplex bead assay analysis.
PVR was induced in all treated eyes (n=6). None of the eyes suffered from intraocular infection. The number of quadrants affected by PVR was 1 (n=3), 2 (n=1), 3 (n=2). TGF-ß1 levels in native eyes were 5.4pg/ml ± 12.0 (AC) and 232.2pg/ml ± 391.1 (vitreous). TGF-ß2 levels in native eyes were 979.3pg/ml ± 48.7 (AC) and 9195.2pg/ml ± 3219.1 (vitreous). During PVR development TGF-ß1 levels increased significantly to 352.8±484.3 (AC) and 1369.2pg/ml ± 1057.3 (vitreous) (p=0.028). TGF-ß2 levels increased to 1655.3±757.1 (AC) and 16134.4pg/ml ± 10348.1 (vitreous). The increase in TGF-ß2 was not significant. TGF-ß3 was not detected at any timepoint. TGF-ß1 but not TGF-ß2 levels in vitreous and AC corresponded well with the amount of PVR and vimentin expression.
The PVR-dependent upregulation of TGF-ß1, and to a lesser extent of TGF-ß2 corresponding to expression of the EMT-marker vimentin may indicate a pivotal role of TGF-ß1 in formation of PVR membranes. TGF-ß1 could therefore be a promising target for inhibition of PVR.
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