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腺相关病毒(AAV)载体递送的内皮抑素对小鼠角膜损伤模型中角膜新生血管形成的抑制作用。

Inhibition of corneal neovascularization with endostatin delivered by adeno-associated viral (AAV) vector in a mouse corneal injury model.

作者信息

Lai Li-Ju, Xiao Xiao, Wu June H

机构信息

Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei San, Tao Yuan, 333, Taiwan.

出版信息

J Biomed Sci. 2007 May;14(3):313-22. doi: 10.1007/s11373-007-9153-7. Epub 2007 Mar 21.

DOI:10.1007/s11373-007-9153-7
PMID:17373573
Abstract

The use of a recombinant adeno-associated viral (rAAV) vector carrying endostatin gene as an anti-angiogenesis strategy to treat corneal neovascularization in a mouse model was evaluated. Subconjunctival injection of recombinant endostatin-AAV was used to examine the inhibition of corneal neovascularization induced by silver nitrate cauterization in mice. The results showed that gene expression in corneal tissue was observed as early as 4 days after gene transfer and stably lasted for over 8 months with minimal immune reaction. Subconjunctival injection of a high-titer rAAV-endostatin successfully inhibited neovascularization. Immunohistchemistry staining of CD 31 and endostatin showed that the treatment significantly inhibits angiogenesis in cornea. We concluded that the rAAV was capable of directly delivering genes to the ocular surface epithelium by way of subconjunctival injection and was able to deliver sustained, high levels of gene expression in vivo to inhibit angiogenesis.

摘要

评估了使用携带内皮抑素基因的重组腺相关病毒(rAAV)载体作为抗血管生成策略治疗小鼠模型角膜新生血管的效果。采用结膜下注射重组内皮抑素-AAV来检测对硝酸银烧灼诱导的小鼠角膜新生血管的抑制作用。结果显示,基因转移后4天即可在角膜组织中观察到基因表达,且能稳定持续8个月以上,免疫反应极小。结膜下注射高滴度rAAV-内皮抑素成功抑制了新生血管形成。CD 31和内皮抑素的免疫组化染色表明,该治疗显著抑制了角膜血管生成。我们得出结论,rAAV能够通过结膜下注射将基因直接递送至眼表上皮,并能够在体内实现持续、高水平的基因表达以抑制血管生成。

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