Noise-induced tinnitus generates reactive oxygen species (free radicals) damaging the neural structures which may be involved in tinnitus generation.
Acoustic trauma triggers a cochlear overstimulation which may cause an excess release of glutamate in the synapse between the inner hair cells and the auditory nerve. An up-regulation of NMDA glutamate receptors may also occur. Both processes occurring simultaneously may in turn lead to a massive Ca2+ release of and activation of pro-apoptotic signaling cascades in the spiral ganglion cells and ultimately cell death decreasing auditory nerve activity.
Latanoprost, and other prostaglandin PGF2α analogues, have been shown to a exert neuroprotective effect, e.g. against glutamate toxicity in retinal ganglion cells. This effect is independent of its effect of lowering intra-ocular pressure through activation of the uveoscleral outflow of ocular fluid. A potential suggested mechanism for its neuroprotective effect has been the suppression of Ca2+ and as a consequence apoptosis.
Salicylate-induced tinnitus has been suggested to be due to excessive arachidonic acid levels due to the blockade of COX1-2. The arachidonic acid would then potentiates the effect of glutamate causing a dysregulation of cochlear NMDA receptors. An alternative interpretation is that the reduced levels of cochlear prostaglandin following COX1-2 inhibition may elicit tinnitus assuming that endogenous PGF2α generated in the cochlea, is important for the normal physiologic hearing process.
All three examples provide appealing potential mechanisms of action and rationale for prostaglandin PF2α intervention in noise-induced tinnitus which is currently under evaluation.