TY - JOUR
T1 - Effect of 2′-benzoyl-oxycinnamaldehyde on RPE cells in vitro and in an experimental proliferative vitreoretinopathy model
AU - Lee, Jae Jun
AU - Park, Jong Kuk
AU - Kim, Yun Taik
AU - Kwon, Byoung Mog
AU - Kang, Shin Goo
AU - Yoo, Young Do
AU - Yu, Young Suk
AU - Chung, Hum
PY - 2002/9
Y1 - 2002/9
N2 - 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 105 rabbit RPE cells were injected into the vitreous cavity after gas compression, and the eyes subsequently received either sham injections or 600 μM BCA. Fundus examination was performed before and 1, 7, 14, 21, and 28 days 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-μM 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.
AB - 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 105 rabbit RPE cells were injected into the vitreous cavity after gas compression, and the eyes subsequently received either sham injections or 600 μM BCA. Fundus examination was performed before and 1, 7, 14, 21, and 28 days 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-μM 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.
UR - http://www.scopus.com/inward/record.url?scp=0036707518&partnerID=8YFLogxK
M3 - Article
C2 - 12202537
AN - SCOPUS:0036707518
SN - 0146-0404
VL - 43
SP - 3117
EP - 3124
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 9
ER -