Thesis, COLLÉGIALITÉ

Abstract

Mutations in extracellular matrix (ECM) related genes have been increasingly associated with hearing impairments in humans. By providing viscoelastic properties to the resonant structures of the inner ear, mechanical and trophic support to the cells and participating in cell signalling in response to environmental changes, the ECM is crucial for hearing function. In this work, we investigated some of its critical regulators namely, Cemip hyaluronidase, and the matrix metalloproteinases, MMP2 and MMP9. By using a mouse model invalidated for Cemip, we studied the hearing function at different ages to analyse whether hyaluronic acid (HA) accumulation could impair audition. Results from auditory brainstem recordings (ABR) reveal no obvious hearing decline in Cemip-deficient mice, up to 16 weeks of age. Future functional studies, up to 1 year of age, will allow us to know if age related hearing loss may be accelerated or exacerbated in the absence of Cemip. However, we can conclude that Cemip, which is defined as a deafness-causing gene in humans, is not essential for hearing in young adult mice. As noise overexposure has been reported to trigger ECM breakdown and remodelling, we characterized MMP2 and MMP9 gelatinases expression and localisation changes in a noise induced hearing loss mouse model. At the level of the whole cochlea, MMP2 transcript level tended to increase from 2 hours to 3 days following noise exposure, while MMP9 transcript tended to decrease progressively from 1 day to 7 days after trauma. Immunostainings revealed that MMP2 protein was upregulated throughout the cochlear tissue as soon as 2 hours following noise, particularly in the surrounding bony capsule but also at the level of the spiral ligament and auditory nerve fibres. In contrast, noise only induced a local accumulation of MMP9 in the spiral ligament. Altogether, our results suggest that MMP2 and MMP9 might be involved in local ECM remodelling after noise exposure, however, further studies are required to verify whether their presence translates into gelatinase activity.