Abstract:
It is well established that supporting cells of the cochlea not only play a large role in structural integrity to maintain sensory transduction, but are also involved in the maintenance of the sensory epithelium, including its repair following death of sensory hair cells. Adenosine Triphosphate (ATP) has recently been proposed as a mediator of hair cell death, in addition to the activation of controlled supporting cell repair processes to expand around a dying hair cell body and eventually engulf it. This is essential for preserving the anatomical and functional integrity of the organ of Corti. This preliminary study aimed to provide further evidence of the role of ATP in both injury and repair processes. In addition, it aimed to gain a greater understanding of the metabolite Adenosine on regulating hair cell survival and maintaining the integrity of the organ of Corti. Tissues from the organ of Corti of P7 mice were dissected and cultured for intervals up to 12 hours in 5 different conditions; Control (culture media only), Neomycin (100μM), ATPγS (100μM), Suramin with ATPγS (100μM each), PPADS with ATPγS (100μM each) and Adenosine with ATPγS (1mM and 100μM, respectively). Whole mounts of the tissue were prepared, labelled with Phalloidin (an actinspecific stain) and imaged using a confocal microscope. The overall appearance of each tissue whole mount was examined and scar formation processes were scrutinised. The preliminary findings suggest purinergic pathways mediate cell death and repair and involve different receptor populations. Cell death pathways may involve P2Y4 whilst repair pathways may primarily involve P2Y2 receptors on supporting cells. Adenosine showed apparent otoprotection of outer hair cells; however this remains to be quantified. Further investigation will assist in confirming the precise mechanisms involved in the damage and repair of the cochlea. Ultimately this knowledge will provide therapeutic targets to alleviate hearing loss affecting millions of people worldwide.