Effects of Transforming Growth Factor-beta on Proliferation, Collagen synthesis, Migration and Metalloproteinase Secretion of Human Retinal Pigment Epithelial Cells

ABSTRACT

PURPOSE: This study was performed to evaluate the effect of TGF-beta on proliferation, collagen synthesis, migration, and matrix metalloproteinase (MMP) secretion of human RPE cells in vitro. METHODS: The cultured human RPE cells were treated with either TGF-beta1 or TGF-beta2 in concentrations of 0, 0.1, 1, 10 ng/ml respectively. The cell number was measured in 3, 6, 9 days, and the collagen synthesis and cell migration was measured. [3H]-thimidine uptake assay was done to evaluate the change of DNA synthesis. And the secretions of MMP1, MMP2, MMP3, MMP9, TIMP1 (tissue inhibitor of metalloproteinase), and TIMP2 were measured by electrophoresis and Western blot analysis. RESULTS: TGF-beta1 and TGF-beta2 significantly inhibited the proliferation of RPE cells in a concentration -and time-dependent manner (p<0.05). [3H]-thymidine uptake was decreased by TGF-beta1 and TGF-beta2 in a concentration-dependant manner. The collagen synthesis of RPE cells was significantly increased by high concentration of TGF-beta1 and TGF-beta 2. However, the migration of RPE cells was not affected by TGF-beta. As the concentration of TGF-beta1 and TGF-beta2 increased, the secretions of MMP1, MMP2, MMP3 and MMP9 decreased, while the secretion of TIMP1 and TIMP2 increased after 72 hours. CONCLUSIONS: These results suggest that the TGF-beta1 and TGF-beta2 may have critical effect on the development of PVR and provide clues to possible therapeutic solutions for controlling PVR process.