Background: Acquired hearing loss (including age-related loss, noise-induced loss and loss associated with clinical drug treatment) is a significant public health issue. The molecular mechanisms resulting in these conditions are poorly understood. However, it is clear that programmed death (apoptosis) of cells within the cochlea is often involved. Through better understanding of the regulation of this process it is hoped that we will identify therapeutic targets for prevention and treatment of acquired hearing loss.
Objectives: To understand the molecular regulation of cell death in the ear so as to identify drug targets for prevention and treatment of hearing loss.
Method: A panel of engineered mouse strains harbouring mutations in apoptotic regulators is being assessed for hearing loss, to better understand the role of cell death in the auditory system.
Results: Mutations at particular points of the intrinsic pathway of apoptosis have a profound effect on the auditory system. Deficiencies of certain apoptotic regulators can disrupt development of the auditory system or result in hearing loss in the adult.
Conclusion: Our work suggests that tightly regulated apoptosis is required for both development and maintenance of hearing. Targeting of apoptotic regulators may prove useful in prevention of cell death and resultant hearing loss in the ear. Future work is planned to test this hypothesis.