Macrophage contribution to the response of the rat organ of corti to amikacin
Macrophage contribution to the response of the rat organ of corti to amikacin
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DOI：
10.1002/jnr.21335
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发表时间：
2007-07-01
影响因子：
4.2
通讯作者：
Lenoir, Marc
中科院分区：
文献类型：
--
作者：
Ladrech, Sabine;Wang, Jing;Lenoir, Marc
非感觉支持细胞向感觉毛细胞的转分化在受损的鸟类内耳中自然发生。通过Atoh 1基因转染，在聋豚鼠耳蜗中实验性地实现了这种转分化。因此，支持细胞可以作为转分化治疗的靶点。然而，支持细胞在毛细胞消失后迅速退化，限制了基因转移的治疗窗口。我们研究了大鼠耳毒性治疗后Deiters细胞（毛细胞支持细胞）超微结构和表型变化的时间过程。还研究了耳蜗中巨噬细胞的存在，以研究它们可能对病理组织产生的任何有害影响。治疗一周后，大部分毛细胞消失。Deiters细胞不再表达神经胶质标志物波形蛋白，而是显示典型的毛细胞标志物，钙结合蛋白和小清蛋白。这表明Deiters细胞转分化为毛细胞的过程被激活。然而，到治疗后3周，Deiters细胞开始退化，到治疗后10周，Corti器官完全降解。有趣的是，在阿米卡星治疗结束后至治疗后10周，巨噬细胞密度显著增加。这表明慢性炎症参与上皮变性。因此，早期使用抗炎因子治疗可能会促进支持细胞的存活，从而提高旨在从非感觉细胞再生毛细胞的更具体策略的功效。(c)2007 Wiley-Liss，Inc.
Transdifferentiation of nonsensory supporting cells into sensory hair cells occurs naturally in the damaged avian inner ear. Such transdifferentiation was achieved experimentally in the cochlea of deaf guinea pigs through Atoh 1 gene transfection. Supporting cells may therefore serve as targets for transdifferentiation therapy. Supporting cells rapidly degenerate after hair cell disappearance, however, limiting the therapeutic window for gene transfer. We studied the time course of ultrastructural and phenotypical changes occurring in Deiters cells (hair cell supporting cells) after ototoxic treatment in the rat. The presence of macrophages in the cochlea was also investigated, to study any deleterious effects they may have on pathologic tissues. One week after treatment most hair cells had disappeared. Deiters cells no longer expressed the glial marker vimentin but instead displayed typical hair cell markers, the calcium binding proteins calbindin and parvalbumin. This suggests that a process of transdifferentiation of Deiters cells into hair cells was activated. By 3 weeks post-treatment, however, the Deiters cells began to degenerate and by 10 weeks post-treatment the organ of Corti was degraded fully. Interestingly, a marked increase in macrophage density was seen after the end of amikacin treatment to 10 weeks post-treatment. This suggests chronic inflammation is involved in epithelium degeneration. Consequently, early treatments with anti-inflammatory factors might promote supporting cell survival, thus improving the efficacy of more specific strategies aimed to regenerate hair cells from nonsensory cells. (c) 2007 Wiley-Liss, Inc.