The semaphorin 3A inhibitor SM-345431 accelerates peripheral nerve regeneration and sensitivity in a murine corneal transplantation model.
The semaphorin 3A inhibitor SM-345431 accelerates peripheral nerve regeneration and sensitivity in a murine corneal transplantation model.
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DOI：
10.1371/journal.pone.0047716
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shimmura S
中科院分区：
文献类型：
--
作者：
Omoto M;Yoshida S;Miyashita H;Kawakita T;Yoshida K;Kishino A;Kimura T;Shibata S;Tsubota K;Okano H;Shimmura S
角膜周围神经损伤是手术或感染后的并发症，可能导致视觉功能下降。我们研究了脑信号蛋白3A抑制剂SM-345431在小鼠角膜移植模型中促进周围神经再生的功效。将在外周神经细胞中表达EGFP的P0-Cre/Floxed-EGFP小鼠用作与同基因野生型小鼠角膜供体的角膜移植的受体。SM-345431每2天结膜下给药一次，而对照小鼠仅接受溶媒。对小鼠进行3周随访，并通过EGFP荧光和针对βIII微管蛋白的免疫组织化学来测量再生神经的长度。角膜敏感性也通过Cochet-Bonnet触觉计测量。使用CD 31染色确定角膜新生血管形成是SM-345431的可能副作用。与对照组相比，SM-345431给药小鼠中βIII微管蛋白阳性周围神经的再生显著更高。此外，移植后3周，SM-345431组的角膜敏感性显著改善。新生血管仅限于外周角膜，SM-345431组和对照组之间无差异。在小鼠角膜移植模型中，结膜下注射SM-345431促进了强大的再生神经网络以及角膜感觉的功能恢复，这表明了治疗神经营养性角膜疾病的新治疗策略。
Peripheral nerve damage of the cornea is a complication following surgery or infection which may lead to decreased visual function. We examined the efficacy of the semaphorin 3A inhibitor, SM-345431, in promoting regeneration of peripheral nerves in a mouse corneal transplantation model. P0-Cre/Floxed-EGFP mice which express EGFP in peripheral nerves cells were used as recipients of corneal transplantation with syngeneic wild-type mouse cornea donors. SM-345431 was administered subconjunctivally every 2 days while control mice received vehicle only. Mice were followed for 3 weeks and the length of regenerating nerves was measured by EGFP fluorescence and immunohistochemistry against βIII tubulin. Cornea sensitivity was also measured by the Cochet-Bonnet esthesiometer. CD31 staining was used to determine corneal neovascularization as a possible side effect of SM-345431. Regeneration of βIII tubulin positive peripheral nerves was significantly higher in SM-345431 treated mice compared to control. Furthermore, corneal sensitivity significantly improved in the SM-345431 group by 3 weeks after transplantation. Neovascularization was limited to the peripheral cornea with no difference between SM-345431 group and control. Subconjunctival injections of SM-345431 promoted a robust network of regenerating nerves as well as functional recovery of corneal sensation in a mouse keratoplasty model, suggesting a novel therapeutic strategy for treating neurotrophic corneal disease.
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