| Title | Antisense oligonucleotide targeting c-fos mRNA limits retinal pigment epithelial cell proliferation; a key step in the progression of proliferative vitreoretinopathy |
| Authors | Zhang, Li Li, Xiaoxin Zhao, Mingwei He, Peiying Yu, Weidong Dong, Jianqiang Liu, Guodong Li, Chunan Shi, Xuan |
| Affiliation | Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China. |
| Keywords | gene therapy c-fos antisense oligonucleotide proliferative vitreoretinopathy retinal pigment epithelium MASSIVE PERIRETINAL PROLIFERATION EXPERIMENTAL-MODEL EXPRESSION RESPONSES MYC |
| Issue Date | 2006 |
| Publisher | experimental eye research |
| Citation | EXPERIMENTAL EYE RESEARCH.2006,83,(6),1405-1411. |
| Abstract | The purpose of this work was to investigate the effect of c-fos antisense oligonucleotide (c-fos-AS-ON) on proliferative vitreoretinopathy (PVR). Cultures of human retinal pigment epithelial (hRPE) cells were established from adult human corneal donors. These cells were positively stained for cytokeratins. C-fos-AS-ON effect on serum-stimulated cell proliferation was estimated by evaluating the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into cellular DNA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were respectively performed to quantify the serum-stimulated c-fos gene mRNA and protein expression in hRPE cells. Eight rabbits (16 eyes) were divided into c-fos-AS-ON treatment group and control group. 2.5 x 10(5) cultured hRPE cells were injected into the vitreous cavity of eyes to establish a PVR model. Prevalence of PVR and retinal detachment were determined by indirect ophthalmoscopy on days 1, 3, 7, 14, 21 and 28 post-injection and by pathological study on days 28 post-injection. The results showed that blocking the expression of c-fos by the addition of c-fos-AS-ON to the culture medium significantly inhibited the hRPE cells proliferation. This effect of c-fos-AS-ON was found to be sequence specific (the use of a sense or a mismatch sense oligonucleotide had no such an effect) and dose-dependent (0.375 mu M was the lowest effective dose tested). Growth inhibition by c-fos-AS-ON remained for at least 72 h. By using RT-PCR and Western blotting, we found that the c-fos-AS-ON could specifically inhibit cfos mRNA and protein synthesis in cultured hRPE cells. Though the eyes injected with c-fos-AS-ON also developed features of PVR, the severities of days 14, 21 and 28 post-injection were significantly lower than those in the control eyes (P < 0.05). We conclude that c-fosAS-ON can inhibit cultured hRPE cell proliferation, which mechanism may relate to blocking the expression of c-fos and can reduce the prevalence of experimental PVR. These findings establish a rationale for investigating the potential use of a c-fos-AS-ON as a novel therapeutical tool in the treatment of PVR. (c) 2006 Elsevier Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/198704 |
| ISSN | 0014-4835 |
| DOI | 10.1016/j.exer.2006.07.020 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 人民医院 |
