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

Jae Jun Lee, Jong Kuk Park, Yun Taik Kim, Byoung Mog Kwon, Shin Goo Kang, Young Do Yoo, Young Suk Yu, Hum Chung

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)3117-3124
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number9
Publication statusPublished - 2002 Sep 1
Externally publishedYes

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Proliferative Vitreoretinopathy
Retinal Pigments
Epithelial Cells
Apoptosis
Rabbits
Injections
Cyclin D
Safety
Phosphotransferases
Down-Regulation
Gases
Phosphorylation
Cell Proliferation
In Vitro Techniques
Staining and Labeling
Therapeutics
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Effect of 2′-benzoyl-oxycinnamaldehyde on RPE cells in vitro and in an experimental proliferative vitreoretinopathy model. / Lee, Jae Jun; Park, Jong Kuk; Kim, Yun Taik; Kwon, Byoung Mog; Kang, Shin Goo; Yoo, Young Do; Yu, Young Suk; Chung, Hum.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 9, 01.09.2002, p. 3117-3124.

Research output: Contribution to journalArticle

Lee, Jae Jun ; Park, Jong Kuk ; Kim, Yun Taik ; Kwon, Byoung Mog ; Kang, Shin Goo ; Yoo, Young Do ; Yu, Young Suk ; Chung, Hum. / Effect of 2′-benzoyl-oxycinnamaldehyde on RPE cells in vitro and in an experimental proliferative vitreoretinopathy model. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 9. pp. 3117-3124.
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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 - 2002/9/1

Y1 - 2002/9/1

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.

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