Effect of Troglitazone to Suppress Proliferation of Human Retinal Pigment Epithelial Cell in vitro and in vivo

Abstract

Purpose: : This study was performed to evaluate the effect of troglitazone, peroxisome–proliferator activated receptor (PPAR) γ agonist, on the cell death of human retinal pigment epithelial cell (RPE) and prevention of proliferative vitreoretinopathy (PVR) in rabbit model.

Methods: : Growth inhibition was measured with MTT assay and apoptosis was observed with FACS scan. Expression of p53, p21, Bcl–2, GADD 45 and Akt1/2 after treating various concentration of troglitazone were acquired with western blot analysis. Intravitreal toxicity was examined with electroretinogram and histologic section of retinal tissue. Using rabbit model of proliferative vitreoretinopathy, antiproliferative effect of trolitazone (300 µM) was measured.

Results: : Troglitazone showed 50% of cell inhibition between 10 and 20 µM concentration. Expression of p53 was increased and that of bcl2 and Akt1/2 were decreased in apoptotic retinal pigment epithelial cells treated with troglitazone. Intravitreal injection of troglitazone effectively suppressed proliferative vitreoretinopathy induced by human retinal pigment epithelial cells in the rabbit eyes. (p= 0.026, Mann–Whitney U–test) No drug related toxicities were observed in these experiments.

Conclusions: : Troglitazone effectively inhibit proliferation of human retinal pigment epithelial cell in vitro and in vivo. Single intravitreal injection of troglitazone is safe and can be effective armament to prevent proliferative vitreoretinopathy.

Keywords: proliferative vitreoretinopathy • retinal pigment epithelium • drug toxicity/drug effects