Secreted Factors from Human Vestibular Schwannomas Can Cause Cochlear Damage.

Sonam Dilwali,Daniel G Deschler,Vitor Y R Soares,Konstantina M Stankovic,Lukas D Landegger

doi:10.1038/srep18599

Abstract

Vestibular schwannomas (VSs) are the most common tumours of the cerebellopontine angle. Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. To establish the first model to study the role of VS-secreted factors in causing SNHL, murine cochlear explant cultures were treated with human tumour secretions from thirteen different unilateral, sporadic VSs of subjects demonstrating varied degrees of ipsilateral SNHL. The extent of cochlear explant damage due to secretion application roughly correlated with the subjects’ degree of SNHL. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Secretions from VSs associated with good hearing or from healthy human nerves led to either no effect or solely fibre disorganization. Our results are the first to demonstrate that secreted factors from VSs can lead to cochlear damage. Further, we identified tumour necrosis factor alpha (TNFα) as an ototoxic molecule and fibroblast growth factor 2 (FGF2) as an otoprotective molecule in VS secretions. Antibody-mediated TNFα neutralization in VS secretions partially prevented hair cell loss due to the secretions. Taken together, we have identified a new mechanism responsible for SNHL due to VSs.

Highlights

Ninety-five percent of people with Vestibular schwannomas (VSs) present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown
VS size correlates with the degree of SNHL, suggesting that mechanical compression may be an important factor in SNHL due to NF2 VSs16, which is why our work focuses on sporadic VS-associated SNHL
Based on the results in the histopathological study of human temporal bones affected by VS10, we focused on hair cell and neurite loss, while testing VS secretions obtained from subjects with different degrees of ipsilateral SNHL

Summary

Introduction

Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Two classes of drugs have demonstrated some efficacy in ameliorating SNHL due to VS via unknown mechanisms: bevacizumab, a monoclonal antibody against vascular endothelial growth factor A (VEGF-A) improves hearing in 54% of NF2-associated VS3, whereas corticosteroids can improve sudden SNHL associated with sporadic and NF2-associated VS4.

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Results

Conclusion