Comparative proteomic analysis of cochlear tissues in guinea pigs and rats

<p dir="ltr">The cochlea is a sensitive biosensor system with the ability to detect sounds that cause movement of the eardrum. These capabilities begin at the mechanically sensitive receptor hair cells, which efficiently translate mechanical stimuli in sound waves into electrical signals that the brain recognises as sound. Damage to hair cells can release proteins and trigger a cascade of biological responses, which may damage hearing function. Mass spectrometry-based proteomics provides powerful tools for improving our understanding of inner ear diseases by elucidating specific alterations of protein expression levels in cochlear tissues. Due to limited access to the human inner ear and the lack of experimental approaches to study the pathophysiology of hearing disorders in animal models, this thesis aims to: 1) Develop a comprehensive proteome profiling for cochlear tissues in healthy guinea pigs and rats with their auditory function closely resembles that of humans, 2) Compare the proteomic profiles between right and left ears and 3) Assess the suitability of guinea pigs and rats as models for studying human inner ear diseases. Experiments first optimised the protein extraction protocol to investigate cochlear protein expression using three biological replicates for each animal model. Results identified a total of 1801 and 3867 proteins in guinea pigs and rats, respectively. Moreover, a high degree of overlap was observed for cochlear protein expression across the left and right ears of each animal, with 93% overlap in guinea pigs and 89% in rats, respectively. Based on the published human data, these results revealed a higher number of shared proteins between humans and rats compared to those shared between guinea pigs. Therefore, rats could be considered viable animal models for research into human inner ear disease. This thesis provides a comprehensive cochlear proteome in guinea pigs and rats, which can facilitate future analysis of ear disorders.</p>