[Show abstract][Hide abstract] ABSTRACT: Chien-Neng Kuo 1,2,3,4, Chung-Yi Chen 5, San-Ni Chen 6,7, Lin-Cheng Yang 8, Li-Ju Lai 1,2,3, Chien-Hsiung Lai 1,2,3, Miao-Fen Chen 2,3,9, Chia-Hui Hung 2,3,10 and Ching-Hsein Chen 11,* 1 Department of Ophthalmology, Chang Gung Memorial Hospital, No.6, W. Sec., Jiapu Rd., Puzi City, Chiayi County 61363, Taiwan; E-Mails: firstname.lastname@example.org (C.-N.K.); email@example.com (L.-J.L.); firstname.lastname@example.org (C.-H.L.) 2 Chang Gung University College of Medicine, No.259, Wenhua 1st Rd., Guishan Township, Taoyuan County 33302, Taiwan; E-Mails: email@example.com (M.-F.C.); firstname.lastname@example.org (C.-H.H.) 3 Chang Gung University of Science and Technology, No.2, W. Sec., Jiapu Rd., Puzi City, Chiayi County 61363, Taiwan 4 Department of Ophthalmology, Changhua Christian Hospital, Yun Lin Branch, No.375, Shichang S. Rd., Xiluo Township, Yunlin County 64866, Taiwan 5 School of Medical and Health Sciences, Fooyin University, No.151, Jinxue Rd., Daliao Dist., Kaohsiung City 83102, Taiwan; E-Mail: email@example.com 6 Department of Ophthalmology, Changhua Christian Hospital. No.135, Nanxiao St., Changhua City, Changhua County 50006, Taiwan; E-Mail: firstname.lastname@example.org 7 School of Medicine, Chung-Shan Medical University, Taichung City 50000, Taiwan 8 Gene Therapy Laboratory, E-DA Hospital, I-Shou University, No.1, Sec. 1, Syuecheng Rd., Dashu District, Kaohsiung City 84001, Taiwan; E-Mail: email@example.com 9 Department of Radiation Oncology, Chang Gung Memorial Hospital, No.6, W. Sec., Jiapu Rd., Puzi City, Chiayi County 61363, Taiwan 10 Department of Dermatology, Chang Gung Memorial Hospital, No.6, W. Sec., Jiapu Rd., Puzi City, Chiayi County 61363, Taiwan 11 Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi City 60004, Taiwan * Author to whom correspondence should be addressed; E-Mail: firstname.lastname@example.org; Tel.: +886-5-362-1000 (ext. 2580); Fax: +886-5-362-3002.
International Journal of Molecular Sciences 04/2013; 14(4):8291-8305. DOI:10.3390/ijms14048291 · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bevacizumab, a recombinant humanized monoclonal antibody, binds vascular endothelial growth factor (VEGF) and inhibits its interaction with receptors found on endothelial cells. Bevacizumab has been increasingly used as an off-label treatment for exudative age-related macular degeneration (AMD). Whether or not bevacizumab is capable of arresting the growth of human retinal pigment epithelial cells remains to be clarified. In this study, flow cytometry was used to evaluate whether bevacizumab markedly induced the G1/S phase arrest. The G1/S phase cycle-related protein analysis demonstrated that the expression of cyclin-dependent kinase (CDK)2, 4 and 6 and of cyclin D and E, as well as the phosphorylation of retinoblastoma tumor suppressor protein (ppRB) production were found to be markedly reduced by bevacizumab. By contrast, the protein levels of p53, p16, p21 and p27 were increased in bevacizumab-treated ARPE-19 cells (a human retinal pigment epithelial cell line). These events of G1/S arrest induced by bevacizumab in ARPE-19 cells suggest that a preventive effect of bevacizumab exists in AMD.
Molecular Medicine Reports 07/2012; 6(4):701-4. DOI:10.3892/mmr.2012.986 · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of Synthetic Amphiphile INTeraction-18 (SAINT-18) carrying plasmid pigment epithelium-derived factor (p-PEDF) as an anti-angiogenesis strategy to treat corneal neovascularization in a rat model was evaluated. Four partially dried forms (Group A: 0 μg, B: 0.1 μg, C: 1 μg, D: 10 μg) of a p-PEDF–SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at the temporal side. The 1 μg of plasmid-basic fibroblast growth factor–-SAINT-18 (p-bFGF–SAINT-18) (1 μg) was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. Inhibition of neovascularization was observed and quantified from day 1 to day 60. PEDF (50-kDa) and bFGF (18-kDa) protein expression were analyzed by biomicroscopic examination, Western blot analysis, and immunohistochemistry. Gene expression in corneal and conjunctival tissue was observed as early as 3 days after gene transfer and stably lasted for over 3 months with minimal immune reaction. Subconjunctival injection of a highly efficient p-PEDF–SAINT-18 successfully inhibited corneal neovascularization. Successful gene expression of bFGF, PEDF and a mild immune response of HLA-DR were shown by immunohistochemistry staining. We concluded that SAINT-18 was capable of directly delivering genes to the ocular surface by way of subconjunctival injection, and delivered sustained, high levels of gene expression in vivo to inhibit angiogenesis.
Experimental Eye Research 11/2009; 89(5):678-685. DOI:10.1016/j.exer.2009.06.021 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a novel vector system of nonviral gene transfer into the cornea using a partially dried form of a plasmid expressing 18-kDa basic fibroblast growth factor (p-bFGF)-synthetic amphiphile INTeraction-18 (SAINT-18) complex.
Corneal neovascularization (NV) was evaluated in 48 eyes of Sprague-Dawley rats after implantation of SAINT-18 containing 2 micro g of plasmid-expressing green fluorescent protein (p-GFP; control group), 0.2 micro g, 2 micro g, or 20 micro g of p-bFGF from day 0 to day 60. bFGF protein expression was analyzed by Western blotting and immunohistochemistry.
The p-bFGF-SAINT-18 complex induced dose-dependent corneal neovascularization, which reached a maximum on days 15-21 in the 20-micro g p-bFGF group, days 12-18 in the 2-micro g p-bFGF group, and on days 9-15 in the 0.2-micro g p-bFGF group, and then regressed progressively. No NV was observed in the p-GFP group.
This noninflammatory corneal transfection model using partially dried p-bFGF-SAINT-18 complex allows precise localization of tranfection reagents for producing corneal neovascularization.
Current eye research 11/2008; 33(10):839-48. DOI:10.1080/02713680802382963 · 1.66 Impact Factor