Abstract
Purpose: :
Proliferative diseases in the eye such as proliferative vitreoretinopathy and proliferative diabetic retinopathy are a major cause of blindness. The fibroblastic change of retinal pigment epithelial cells (RPE) and vitreous cells induce fibroblastic membrane, and ultimately carry out tractional retinal detachment via contraction. This current study was conducted to examine the feasibility of using the Peroxisome Proliferator-Activated Receptor γ (PPARγ) agonist as a therapeutic tool for proliferative diseases.
Methods: :
Human RPE cells (ARPE-19) and rabbit vitreous cells were cultured. The culture medium was then replaced with fresh TGF-β2 (5ng/ml) medium with PPARγ agonist (3, 10, and 30 µM). Culture medium containing TGF-β2 without PPARγ agonist was used for the control. Cell morphology was examined by phase contrast microscopy after 24 and 48 hours of incubation. As an in vitro contraction model, ARPE-19 and rabbit vitreous cells are cultured in collagen gels at the density of 5×105 cells/mm2. The culture medium was then replaced with fresh medium containing TGF-β2 with or without PPARγ agonist (3, 10, and 30µM). The collagen gel contraction was evaluated by Image J software after 5 days of incubation.
Results: :
The fibroblastic changes of both ARPE-19 and vitreous cells were suppressed by 10- and 30µM of PPARγ agonist, while fibroblastic change was observed in the control cells. In the in vitro contraction model, contraction induced by TGF-β2 was not observed in ARPE-19, but was observed in vitreous cells. The mean area of the collagen gels in the TGF-β2 with PPARγ agonist group (30µM) was 77.5%, while those in the TGF-β2 group was 66.5% as a ratio of the initial area, respectively.
Conclusions: :
The results of this study demonstrate that PPARγ agonist inhibits the fibrotic change both of RPE and vitreous cells, and especially suppresses the contraction of vitreous cells. We speculate that PPARγ agonist will be an applicable pharmaceutical treatment for proliferative diseases in the eye.
Keywords: retinal pigment epithelium • EMT (epithelial mesenchymal transition) • drug toxicity/drug effects