The Effects of Tranilast(R) on the Cellular Proliferation, Collagen Synthesis, and Secretion of TGF-beta1 in Bovine Retinal Pigment Epithelial Cells

Lee, Jong Soo; Shin, Young Gun; Jung, Jae Ho; Oum, Boo Sup

Abstract

PURPOSE
To evaluate the effects of Tranilast(R) on the cellular proliferation, collagen synthesis, and secretion of transforming growth factor-beta1 on retinal pigment epithelial cells that influence the development of proliferative vitreoretinopathy in vitro. METHODS: After bovine RPE cells were isolated, they were exposed to Tranilast(R) 0.05, 0.1, 0.2, 0.4, 0.8, 1.0, 1.6 mg/ml and only DMEM which was used as control. MTT was used as a measurement of metabolic activity, and collagen synthesis and TGF-beta1 secretion were assayed by collagen kit (Sigma, USA) and TGF-beta1 kit (Gibco, USA). Western blot assay was used to confirm TGF-beta1, which was expressed by treated Tranilast(R) in bovine RPE cells. RESULTS: The higher the concentration of Tranilast(R), the more the inhibition of the cellular proliferation. LD50 concentration was about 1.0 mg/ml, and there was more significant difference the concentration of over Tranilast(R) 0.4 mg/ml than control (P<0.05). The higher the concentration of Tranilast(R), the more the inhibition of collagen synthesis and TGF-beta1 secretion from RPE cells, especially over Tranilast(R) 0.05 mg/ml (P<0.05). There was no response of TGF-beta1 expression in the concentration of Tranilast(R) 0.2 mg/ml compared to untreated bovine retinal epithelial cells. CONCLUSIONS: Tranilast(R) has a tendency of inhibitory effect in the cellular proliferation, collagen synthesis, and TGF-beta1 secretion. Tranilast(R) may prevent excessive proliferation of RPE and scar formation concerned with collagen synthesis and TGF-beta1 secretion in the proliferative vitreoretinal diseases.