Department of Otorhinolaryngology, Hannover Medical School, Hannover, Germany.
Hearing4all Cluster of Excellence, Hannover Medical School, Hannover, Germany.
Audiol Neurootol. 2023;28(1):43-51. doi: 10.1159/000526454. Epub 2022 Sep 8.
Loss of hair cells and degeneration of spiral ganglion neurons (SGN) lead to severe hearing loss or deafness. The successful use of a cochlear implant (CI) depends among other factors on the number of surviving SGN. Postoperative formation of fibrous tissue around the electrode array causes an increase in electrical impedances at the stimulating contacts. The use of immunophilin inhibitors may reduce the inflammatory processes without suppressing the immune response. Here, we report on in vitro experiments with different concentrations of immunophilin inhibitors MM284 and compound V20 regarding a possible application of these substances in the inner ear.
Standard cell lines (NIH/3T3 fibroblasts), freshly isolated SGN, and fibroblasts from neonatal rat cochleae (p3-5) were incubated with different concentrations of immunophilin inhibitors for 48 h. Metabolic activity of fibroblasts was investigated by MTT assay and cell survival by counting of immunochemically stained neurons and compared to controls.
MM284 did not affect SGN numbers and neurite growth at concentrations of 4 × 10-5 mol/L and below, whereas V20 had no effect at 8 × 10-6 mol/L and below. Metabolic activity of fibroblasts was unchanged at these concentrations.
Especially MM284 might be considered as a possible candidate for application within the cochlea.
毛细胞和螺旋神经节神经元（SGN）的丧失会导致严重的听力损失或耳聋。耳蜗植入物（CI）的成功使用取决于其他因素，包括存活的 SGN 数量。电极阵列周围纤维组织的术后形成会导致刺激触点的电阻增加。免疫亲和素抑制剂的使用可以减少炎症过程，而不会抑制免疫反应。在这里，我们报告了不同浓度的免疫亲和素抑制剂 MM284 和化合物 V20 的体外实验结果，这些物质可能在内耳中有应用。
用不同浓度的免疫亲和素抑制剂 MM284 和化合物 V20 孵育标准细胞系（NIH/3T3 成纤维细胞）、新鲜分离的 SGN 和来自新生大鼠耳蜗的成纤维细胞（p3-5）48 小时。通过 MTT 测定法研究成纤维细胞的代谢活性，并通过免疫化学染色神经元的计数来研究细胞存活情况，并与对照组进行比较。
在浓度为 4×10-5 mol/L 及以下时，MM284 不会影响 SGN 数量和神经突生长，而 V20 在浓度为 8×10-6 mol/L 及以下时没有影响。这些浓度下成纤维细胞的代谢活性没有变化。
特别是 MM284 可能被认为是耳蜗内应用的候选药物。
