Effect of 2 '-benzoyl-oxycinnamaldehyde on RPE cells in vitro and in an experimental proliferative vitreoretinopathy model

Abstract

Purpose. To investigate whether 2'-benzoyl-oxycinnamaldehyde (BCA) induces apoptosis in human retinal pigment epithelial (hRPE) cells and has an antiproliferative effect in a proliferative vitreoretinopathy (PVR) model in the rabbit. METHODS. Fifty percent growth inhibition doses of hRPE cells at 50%, 75%, and 100% confluence were determined by MTT assay. Apoptosis in hRPE cells induced by BCA was shown by DAPI staining. Expression of P53, p21, Bcl-2, GADD45, cyclin D, phospho-MAP kinase, cdk2, and Akt1 at various concentrations of BCA in cultured hRPE cells was examined by immunoblot analysis. In the efficacy study, 2.0 x 10(5) rabbit RPE cells were injected into the vitreous cavity after gas compression, and the eyes subsequently received either sham injections or 600 muM BCA. Fundus examination was performed before and 1, 7, 14, 21, and 28 clays after BCA injection. The toxicity studies were conducted by the same protocol as used for the efficacy evaluation but without the RPE cell injection. Simultaneous electroretinograms were recorded on days 1, 7, 14, 21, and 28 after exposure to the drug. RESULTS. BCA treatment induced apoptosis in hRPE cells. Furthermore, an increase in p53 expression, phosphorylation of Bcl-2, and downregulation of Akt1 expression were observed in BCA-induced apoptotic cells. BCA effectively prevented the proliferation of rabbit RPE cells in the experimental PVR model. BCA exhibited a wide safety margin, showing no evidence of causing retinal toxicity, even at the 600-muM concentration CONCLUSIONS. The results of this study suggest that BCA effectively inhibits proliferation of RPE cells and has a very wide safety margin, indicating a potential therapeutic usefulness in treating PVR.