The Role of Adenosine-5’-Triphosphate and Adenosine in Scar Formation in the Neonatal Mice Organ of Corti

Abstract

The World Health Organization reports that over 5% of the world’s population suffer from significant hearing loss. Exposure to excessive noise, use of ototoxic substances and aging can cause damage to cochlear structures and lead to permanent sensorineural hearing loss. Significant hearing loss can have an impact not only on the quality of life but also on the psychosocial wellbeing of an individual. Unfortunately, there is still no known cure for this condition. This study was undertaken to provide a better understanding of the mechanisms behind cochlear injury and repair using the neonatal mouse cochlea as a model. The study focussed on the effects of ATP and adenosine on cochlear tissues and described the morphological changes associated with hair cell injury and supporting cell scar formation. Neonatal cochlear explants obtained from seven-day old mice were incubated for 24 hours in culture media containing ATPS alone or in combination with either an A1 receptor agonist or antagonist. Confocal scanning microscopy was used to visualize the tissues following fixation and then staining with phalloidin. Qualitative analysis was performed on the middle turn of the cochlea by examining hair cell and supporting cell morphology. Introduction of ATPS resulted in hair cell loss with accompanying scar formation suggesting the possible role of ATP in mediating cell death and tissue repair. While A1 receptor activation did not seem to affect scar formation, it appeared to protect outer hair cells, but not inner hair cells, from cochlear damage. Furthermore, the apparent greater susceptibility of inner hair cells to injury suggests different adenosine signalling pathways may be present in the hair cells. The results not only support the possible roles of ATP and adenosine in the processes mediating hair cell death and repair but also underscore the critical role played by supporting hair cells in these processes. The evidence from this study provides a preview of the possible pathophysiological processes involved in the cochlear responses to injury, and hopefully leads to the development of therapeutic strategies against the damaging effects of otologic stresses on the inner ear. Key words: purinergic signalling, ATP, adenosine, cochlea, scar formation