Cationic nano-copolymers mediated IKKβ targeting siRNA to modulate wound healing in a monkey model of glaucoma filtration surgery
| Autor: | Ye, Hehua, Qian, Yiyong, Lin, Mingkai, Duan, Yongheng, Sun, Xuerong, Zhuo, Yehong, Ge, Jian |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Wound Healing
genetic structures Cell Survival Polymers Mitomycin Down-Regulation Endothelial Cells Cell Count Glaucoma Haplorhini Fibroblasts Transfection eye diseases I-kappa B Kinase Disease Models Animal Cations Filtering Surgery Animals Nanoparticles Biological Assay sense organs RNA Small Interfering Research Article Cell Proliferation |
| Zdroj: | Molecular Vision |
| ISSN: | 1090-0535 |
| Popis: | Purpose To investigate the efficacy and safety of cationic nano-copolymers CS-g-(PEI-b-mPEG) mediated IκB kinase beta (IKKβ) targeting siRNA in modulating wound healing in a monkey model of glaucoma filtration surgery. Methods The IKKβ targeting siRNAs were chemically synthesized and screened in cultured monkey Tenon’s fibroblasts in vitro. Fourteen monkeys underwent trabeculectomy and were randomly allocated to one of three treatment regimens: subconjunctival injection of either CS-g-(PEI-b-mPEG)/IKKβ-siRNA (six eyes, 50nM, at the time of surgery and 7 days post surgery) or phosphate buffered saline (four eyes), or treated with mitomycin C (MMC; four eyes, 0.2 mg/ml). Bleb survival and characteristics, and intraocular pressure, were evaluated over a 60-day period. Histology of the surgical eyes was performed to evaluate ocular scarring and fibrosis in each group. Results Subconjunctival injection of CS-g-(PEI-b-mPEG)/IKKβ-siRNA was well tolerated in this model. Both siRNA and MMC significantly prolonged bleb survival compared with the PBS group (the medians for survival days were 45.5, 60, and 29.5 in the siRNA, MMC, and PBS groups, respectively, p0.05). The histologic examination demonstrated that the eyes treated with siRNA showed a marked reduction in subconjunctival scar tissue compared with the eyes in the PBS group. The conjunctival epithelium appeared healthy without the acellularity that was present in the MMC group. Conclusions Subconjunctival injection of cationic nano-copolymers mediated IKKβ targeting siRNA is associated with improved surgical outcome in a monkey model of trabeculectomy. This novel approach may potentially be a more controlled alternative as an anti-scarring agent in glaucoma filtration surgery. |
| Databáze: | OpenAIRE |
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