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Hiroki Hatanaka, Noriko Koizumi, Naoki Okumura, EunDuck P. Kay, Eri Mizuhara, Junji Hamuro, Shigeru Kinoshita; Epithelial-Mesenchymal Transition-Like Phenotypic Changes of Retinal Pigment Epithelium Induced by TGF-β Are Prevented by PPAR-γ Agonists. Invest. Ophthalmol. Vis. Sci. 2012;53(11):6955-6963. doi: 10.1167/iovs.12-10488.
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Proliferative eye diseases, such as proliferative vitreoretinopathy and proliferative diabetic retinopathy, are caused partly by fibrotic change of retinal pigment epithelial cells (RPECs). The purpose of our study was to examine the effect of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist on the fibrotic change of primate RPECs.
Monkey RPECs (MRPECs) isolated from a cynomolgus monkey eye were subcultured. To induce fibrotic change, MRPECs were cultured with TGF-β2 (3 ng/mL), and also cultured in the coexistence of TGF-β2 and the PPAR-γ agonist pioglitazone (30 μM). The phenotype of the cultured MRPECs was evaluated by phase contrast microscopy and immunocytochemical analysis. The phosphorylation of Smad2/Smad3 proteins was examined by Western blot analysis.
Primary MRPECs were cultured as a monolayer with a hexagonal cell shape, and positive expression of ZO-1, Na+/K+-ATPase, and RPE65 was confirmed. Cell morphology and the expression of these markers were maintained in the presence of pioglitazone, whereas the cells were elongated and the expression of these markers was reduced in its absence. Conversely, the expression of phalloidin, α-smooth muscle actin, and fibronectin was reduced in the presence of pioglitazone, whereas it was increased in the absence. Western blot assay demonstrated that phosphorylation of Smad2/Smad3 proteins was suppressed by pioglitazone.
The PPAR-γ agonist pioglitazone inhibited the fibrotic change of primary MRPECs through the suppression of TGF-β signaling. Pioglitazone might prove to be a clinically applicable and effective pharmaceutic treatment for proliferative eye diseases.
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