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日本庆应义塾大学教授冈野荣之率领的研究小组最新发现,一种化合物能促进被切断的角膜感觉神经再生。
角膜有丰富的感觉神经,但在近视矫正、角膜移植等手术中,感觉神经可能被切断,感染也可能破坏神经,损害患者的视力。通常感觉神经再生需要数个月至一两年左右时间,促进神经再生则能改善症状。
研究小组注意到,一种称为“臂板蛋白3A”(sema3A)的蛋白质会遏制神经生长。他们从土壤的霉菌中提取出能抑制这种蛋白质功能的化合物SM-345431,给移植角膜的实验鼠注射。约3周后检查发现,角膜的感觉神经已经再生,而对照组的实验鼠则没有这种现象。
目前,研究人员正在使用诱导多功能干细胞(iPS细胞)等研究实现角膜的再生,而要想使移植的角膜发挥功用,就必须使神经再生。冈野等人在新一期《科学公共图书馆综合卷》报告研究小组指出:“这种化合物将来有可能作为治疗药物,提高角膜移植的成功率,从而有助于对角膜手术的术后管理。(新华网)
原文见:
The Semaphorin 3A Inhibitor SM-345431 Accelerates Pe**heral Nerve Regeneration and Sensitivity in a Murine Corneal Transplantation Model
Masahiro Omoto, Satoru Yoshida, Hideyuki Miyashita, Tetsuya Kawakita, Kenji Yoshida, Akiyoshi Kishino, Toru Kimura, Shinsuke Shibata, Kazuo Tsubota, Hideyuki Okano, Shigeto Shimmura
Background Pe**heral 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 pe**heral nerves in a mouse corneal transplantation model. Methodology/Principal Findings P0-Cre/Floxed-EGFP mice which express EGFP in pe**heral 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 pe**heral 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 pe**heral cornea with no difference between SM-345431 group and control. Conclusions/Significance 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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