Effect of Tranilast on Proliferation, Collagen Gel Contraction, and Transforming Growth Factor Beta Secretion of Retinal Pigment Epithelial Cells and Fibroblasts

Abstract

The efficiency of tranilast for the treatment of proliferative vitreoretinopathy (PVR) was investigated in vitro. A tetrazolium-based colorimetric assay showed that the 300-µM concentration of tranilast inhibited proliferation of bovine retinal pigment epithelial (RPE) cells and rabbit dermal fibroblasts with no toxicity. The contraction of collagen gels embedded with these cells was evaluated in the cultures. Compared with the gel incubated with minimal essential medium and 0.35% bovine serum albumin and/or fetal calf serum, tranilast inhibited gel contraction. Enzyme-linked immunosorbent assay revealed that a 300-µM concentration of tranilast inhibited transforming growth factor-β₁ (TGF-β₁) secretion significantly (p < 0.01). These results suggest that tranilast may inhibit the proliferation of RPE cells and fibroblasts and contraction of intraocular fibrous membranes by suppressing TGF-β₁ secretion from these cells with a potential to treat PVR.

Tranilast: A review of its therapeutic applications

“…Studies conducted on the proliferation of various fibroblasts showed that tranilast inhibited; mouse gastric fibroblasts [54], human pterygium-derived fibroblasts [55], rabbit dermal fibroblasts [56], gingival fibroblasts [57] and fibrous tissue in oral squamous cell carcinomas in mice [58]. It suppressed the content of collagen in granulation tissue of hypersensitive granulomatous inflammation [59].…”

“…Since then, its inhibitory effects have been reported on the proliferation of a range of cell types: dermal fibroblasts [56,75], myofibroblasts [59], microvascular endothelial cells [76], vascular smooth muscle cells [77,78], and mesangial cells [79]. In addition to normal cells, tranilast exerts an anti-proliferative influence on several tumor cells, such as; smooth muscle cells hyperplasia [80], pancreatic cancer cells [81], uterine leiomyoma cells [82], malignant glioma cells [83], gastric cancer cells [84,85], prostate cancer cells [86], breast cancer cells [87][88][89], neurofibroma cells [90] and squamous cell carcinoma [58].…”

Reduction of Post-Surgical Adhesion Formation with Tranilast

“…Mast cells are important early mediators of intraperitoneal inflammation after surgery [29,30]; mast cell stabilization may be an important part of the mechanism of action of tranilast in adhesion prevention. Tranilast was subsequently found to inhibit cell proliferation [23,24,31,32], including vascular smooth muscle cells, which lead to its preclinical [25] and clinical testing as an anti-restenosis agent. In addition to its anti-proliferative effects, tranilast can inhibit various inflammatory responses [33][34][35], TGF-␤ production [26], and collagen production [36], all of which would be expected to negatively impact adhesion formation [37,38].…”

“…This drug inhibits TGF-␤ expression, a known contributor to post-surgical adhesion formation [22][23][24][25][26]. Previous studies by others have demonstrated reduction in adhesions in a rat model using p.o.…”

Curcumin inhibits human retinal pigment epithelial cell proliferation

“…Although controversial, some clinicians have used the intravitreal or systemic injection of steroids to inhibit cell proliferation with poor efficacy (20,21). In addition, although the inhibition of RPE cell proliferation in vitro has been achieved using tranilast (22), genistein (23), ciprofloxacin (24), vitamin C (25), vitamin E (26), minoxidil (27), hypericin (28), cis -hydroxyproline (29), retinoic acid (25), cis -vitamin A acid, aclacinomycin A (30), daunorubicin (31) and N,N-dimethyl doxorubicin (32), many of these drugs have side effects, which significantly limit their wide application in clinical practice.…”