tranilast and Glaucoma

To analyze the release kinetics and the clinical and histological effects of UV-cross-linked hyaluronic acid as a release-system for the transforming growth factor β-2 antagonist tranilast with anti-phlogistic properties on intraocular pressure after trabeculectomy in an aggressive scarring animal model.. Hyaluronate acid was UV-cross linked and loaded with tranilast. The release of tranilast into a buffered salt solution was assessed spectrophotometrically. Glaucoma filtration surgery, similar to that performed in clinical practice, was performed on chinchilla rabbits. The rabbits were divided in 3 groups. (Group A: trabeculectomy alone, group B: trabeculectomy with a cross-linked hyaluronic acid gel preparation and group C: trabeculectomy with cross-linked hyaluronic gel preparation mixed with tranilast). Antifibrotic efficacy was established by clinical response and histologic examination.. The cross-linked gels released tranilast for up to 26 h. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. Both the gel preparation alone and the gel preparation mixed with tranilast were well tolerated in vivo. No adverse effects such as inflammation, corneal toxicity or blurring of the optical media were observed. The intraocular pressure reached preoperative levels within 9 days after surgery in control animals and group B, but remained significantly reduced (p = 0.00016) in the group with tranilast until day 22.. The data of this pilot study suggest that the intraoperative application of UV-crossed linked hyaluronic acid used as a slow release system for tranilast may improve the surgical outcome of glaucoma filtration surgery.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biocompatible Materials; Cell Proliferation; Cross-Linking Reagents; Drug Delivery Systems; Fibrosis; Glaucoma; Hyaluronic Acid; ortho-Aminobenzoates; Pilot Projects; Rabbits; Trabeculectomy; Ultraviolet Rays; Viscosupplements

To investigate the effect of tranilast, N-(3,4-dimethoxycinnamoyl) anthramilic acid, on the proliferation and migration of human Tenon's capsule fibroblasts.. fibroblasts were cultured from Tenon's tissue of a glaucoma patient after trabeculectomy. The subcultured cells were incubated with DMEM medium containing different concentrations of tranilast for 72 h. The growth of fibroblasts was measured by methyl thiazlyl tetrazolium (MTT) assay and the cell count, and migration was evaluated by crutch method. The expression level of Protein kinase C (PKC) in fibroblasts was tested by immunohistochemical associated with image biological analysis (IBAS) methods.. Treated with tranilast varying from 12.5 mg/L to 100.0 mg/L concentration, the proliferation of fibroblasts declined in a dose dependent manner. The migration of fibroblasts decreased from 40.20 +/- 5.83 to 22.50 +/- 4.21 and 9.80 +/- 2.14 cells/per field (P < 0.05) at 50.0 and 100.0 mg/L, respectively, and PKC expression was suppressed by tranilast from 0.2591 +/- 0.0038 to 0.2375 +/- 0.0106 and 0.1273 +/- 0.0573 Absorption value (P < 0.05) at 50.0 and 100.0 mg/L, respectively.. Tranilast inhibited the proliferation as well as migration of fibroblasts in vitro, at least in part, by downregulation of PKC expression.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Movement; Cell Proliferation; Cells, Cultured; Eye; Fibroblasts; Glaucoma; Humans; ortho-Aminobenzoates; Protein Kinase C