(A817) Evaluating Two Novel Compounds for Hearing Preservation in Cochlear Implantation: An Ex Vivo Study

Introduction: Cochlear implantation involves electrode array insertion into the cochlea, which can cause trauma and damage sensory hair cells, leading to residual hearing loss. This study assessed and compared the otoprotective effects of two novel compounds, Compound Y and Compound Z, in mitigating electrode insertion trauma (EIT) using an ex vivo organ of Corti (OC) model. Optimal dosages for effective protection were also determined.

Methods: Organ of Corti specimens from postnatal day 3 rats were assigned to four experimental groups: (1) untreated control, (2) EIT alone, (3) EIT with varying concentrations of Compound Y, and (4) EIT with varying concentrations of Compound Z. EIT was induced by inserting a custom-designed electrode into the cochlea through a cochleostomy near the round window (insertion angle: 110°–150°). Hair cell viability was assessed using FITC-phalloidin staining, while inflammation and apoptosis were evaluated via proinflammatory cytokine quantification and cleaved caspase-3 immunostaining.

Results: EIT caused significant hair cell loss in the OC. Treatment with Compound Y significantly reduced hair cell loss compared to Compound Z. Organs of Corti treated with Compound Y retained more viable hair cells. EIT increased proinflammatory cytokines and apoptosis, as indicated by elevated cleaved caspase-3 levels. Compound Y was more effective than Compound Z in reducing inflammation and apoptosis.

Conclusions: Compound Y demonstrated promising otoprotective effects, reducing sensory cell loss, inflammation, and apoptosis following EIT. This suggests its potential as a therapeutic agent for hearing preservation in cochlear implant recipients. The ex vivo model used in this study provides a valuable platform for exploring interventions to prevent hearing loss. Future research will evaluate Compound Y’s efficacy in in vivo preclinical cochlear implantation models.