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

Inhibition of corneal neovascularization with endostatin delivered by adeno-associated viral (AAV) vector in a mouse corneal injury model
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DOI:
10.1007/s11373-007-9153-7
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发表时间:
2007-05-01
影响因子:
11
通讯作者:
Wu, June H.
Wu, June H.
中科院分区:
医学1区
文献类型:
--
作者:
Lai, Li-Ju;Xiao, Xiao;Wu, June H.

文献摘要

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利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,在小鼠模型中治疗角膜新生血管。采用重组内皮抑素aav结膜下注射法观察硝酸银烧灼对小鼠角膜新生血管的抑制作用。结果表明,基因移植后第4天就可在角膜组织中观察到基因表达,并稳定持续8个月以上,免疫反应最小。结膜下注射高滴度raav -内皮抑素成功抑制新生血管。cd31和内皮抑素免疫组化染色显示,该治疗可显著抑制角膜血管生成。我们得出结论,rAAV能够通过结膜下注射直接将基因传递到眼表上皮,并能够在体内持续高水平地表达基因以抑制血管生成。
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.