Langlie Jake, Mittal Rahul, Elisha David H, Cooper Jaimee, Marwede Hannah, Purrinos Julian, Tuset Maria-Pia, McKenna Keelin, Zalta Max, Mittal Jeenu, Eshraghi Adrien A
Hearing Research and Cochlear Implant Laboratory, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
J Clin Med. 2025 Jul 18;14(14):5115. doi: 10.3390/jcm14145115.
Cochlear implantation is widely used to provide auditory rehabilitation to individuals with severe-to-profound sensorineural hearing loss. However, electrode insertion during cochlear implantation leads to inner ear trauma, damage to sensory structures, and consequently, loss of residual hearing. There is very limited information regarding the target proteins involved in electrode insertion trauma (EIT) following cochlear implantation. The aim of our study was to identify target proteins and host molecular pathways involved in cochlear damage following EIT utilizing the iTRAQ™ (isobaric tags for relative and absolute quantification) technique using our ex vivo model. The organ of Corti (OC) explants were dissected from postnatal day 3 rats and subjected to EIT or left untreated (control). The proteins were extracted, labelled, and subjected to ultra-high performance liquid chromatography-tandem mass spectrometry. We identified distinct molecular pathways involved in EIT-induced cochlear damage. Confocal microscopy confirmed the expression of these identified proteins in OC explants subjected to EIT. By separating the apical, middle, and basal cochlear turns, we deciphered a topographic array of host molecular pathways that extend from the base to the apex of the cochlea, which are activated post-trauma following cochlear implantation. The identification of target proteins involved in cochlear damage will provide novel therapeutic targets for the development of effective treatment modalities for the preservation of residual hearing in implanted individuals.
人工耳蜗植入被广泛用于为重度至极重度感音神经性听力损失患者提供听觉康复。然而，人工耳蜗植入过程中的电极插入会导致内耳创伤、感觉结构受损，进而导致残余听力丧失。关于人工耳蜗植入后电极插入创伤（EIT）所涉及的靶蛋白的信息非常有限。我们研究的目的是利用我们的体外模型，采用iTRAQ™（相对和绝对定量等压标签）技术，鉴定EIT后耳蜗损伤所涉及的靶蛋白和宿主分子途径。从出生后第3天的大鼠中分离出柯蒂氏器（OC）外植体，对其进行EIT处理或不进行处理（对照）。提取蛋白质、进行标记，然后进行超高效液相色谱-串联质谱分析。我们鉴定出了EIT诱导的耳蜗损伤所涉及的不同分子途径。共聚焦显微镜证实了这些鉴定出的蛋白质在接受EIT处理的OC外植体中的表达。通过分离耳蜗的顶部、中部和基部蜗旋，我们解读了从耳蜗基部延伸至顶部的宿主分子途径的地形图，这些途径在人工耳蜗植入后的创伤后被激活。鉴定出参与耳蜗损伤的靶蛋白将为开发有效的治疗方法以保留植入个体的残余听力提供新的治疗靶点。
