Can synaptic damage and hearing loss be reversed?

Progressive hearing loss is very common but there are no medical treatments to slow down or reverse it.

In this project, we will investigate whether it is possible to reverse hearing loss and if so, whether there is a critical period after which reversal no longer occurs.

We propose to analyse a mouse mutant, Pex3tm1a, that shows progressive loss of auditory sensitivity associated with disruption of inner hair cell synapses.

We will use a conditional tamoxifen-inducible Flp recombinase allele to reactivate the mutant Pex3 gene after onset of hearing loss, and compare Auditory Brainstem Responses before and after exposure to tamoxifen.

We will investigate any limiting factors to reversal of hearing loss such as hair cell degeneration and how these define the critical period for intervention.

Inner hair cell synapses will be analysed by immunolabelling and confocal microscopy to look for any evidence that they may reconnect after reactivation of the Pex3 gene.

Finally, as Pex3 is required for peroxisome biosynthesis and these organelles have been implicated in susceptibility to noise damage, we will ask if Pex3 mutants are especially sensitive to noise.