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Hiroki Hatanaka, Naoki Okumura, Noriko Koizumi, Eri Mizuhara, Hiroatsu Hirano, Junji Hamuro, Shigeru Kinoshita; Effect of SAHA on Fibrotic Change in Primate Retinal Pigment Epithelium Cells and Vitreous Cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6260.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative eye diseases such as proliferative vitreoretinopathy and proliferative diabetic retinopathy are a major cause of blindness. The fibroblastic change of retinal pigment epithelial (RPE) cells and vitreous cells induce fibroblastic membrane, and ultimately carry out tractional retinal detachment via contraction. The purpose of this present study was to examine the feasibility of using suberoylanilide hydroxamic acid (SAHA) as a therapeutic tool for proliferative diseases using primary cultured primate RPE cells and rabbit vitreous cells.
As in the method described in our previous reported (Invest Ophthalmol Vis Sci 53: 6995-6963, 2012.), monkey RPE (MRPE) cells were isolated from the eyes of a cynomolgus monkey and then subcultured with culture medium containing 2% fetal bovine serum. MRPE cells and rabbit vitreous cells were then cultured. The culture medium was then replaced with fresh TGF-β2 (3ng/ml) medium with SAHA (300, 1000, and 3000 nM). Culture medium containing TGF-β2 without SAHA was used for the control. Cell morphology was examined by phase contrast microscopy after 48 hours of incubation. As an in vitro contraction model, rabbit vitreous cells were 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 SAHA (3, 10, and 30 μM). The collagen gel contraction was then evaluated by Image J software after 5 days of incubation.
The fibroblastic change of MRPE cells were suppressed by 1000 nM of SAHA, while fibroblastic change was observed in the control cells. The incidence of fibrotic MRPE cells was significantly reduced from 38.6±1.3% in the TGF-β2 group to 9.3±1.3% in the TGF-β2 with SAHA group. 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 SAHA group (30µM) was 77.6%, while that in the TGF-β2 group was 66.0% as a ratio of the initial area, respectively (p<0.05).
The results of this study demonstrate that SAHA inhibits the fibrotic change of RPE cells and the contraction of vitreous cells. We speculate that SAHA will become an applicable pharmaceutical treatment for proliferative eye diseases.
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