![Peihan Orestes, Ph.D.]()
University of California, Los Angeles
Cellular modifications of the vestibular labyrinth: Intrinsic mechanisms following unilateral aminoglycoside treatment for Meniere’s disease
Intra-tympanic gentamicin is a widely used treatment for unilateral Meniere’s disease, primarily to reduce the activity in the affected ear and thereby reduce the frequency and severity of vertigo attacks. Though the treatments are applied to only one ear, the adaptive effects in the untreated ear have not been widely studied. At the same time, there is evidence indicating that the vestibular receptors exhibit intrinsic capabilities for modification or adaptation to alterations from the normal operating conditions. For example, the inner ear vestibular receptors may undergo a form of “sensory learning” when exposed to changes in the ambient operating conditions associated with spaceflight. An investigation of the contralateral labyrinth following treatments comparable to that associated with intra-tympanic gentamicin may provide clues as to alterations in the conserved ear. These capabilities may be recruited through rehabilitative measures (pharmacologic, physical therapy) to accelerate recovery to normal vestibular function. We propose to study the activity of individual neurons projecting to the conserved vestibular receptors, thereby providing a direct measure of the output of these neurons and by comparisons to our large database of untreated specimens, as well as to determine whether alterations in this activity ensues following adaptation to administration of gentamicin to the contralateral ear.
Research area: Meniere's disease; Ototoxicity
Long-term goal of research: The proposed work is based on the intra-tympanic gentamicin treatment currently used for Ménière’s disease, but the implications of this study could have an even greater impact. Better understanding of the vestibular system’s ability to respond to damage reveals the possibility of retraining the non-lesioned ear, akin to physical therapy. Though most animal studies use unilateral labyrinthectomy as their disease model, such complete loss is rare in the clinical setting. The intra-tympanic gentamicin treatment for Ménière’s disease is not the same as a labyrinthectomy, as the lesions are likely to be partial. Thus, the experiment described here, a direct test of whether peripheral plasticity ensues following partial lesions, is more translationally realistic compared to the labyrinthectomy. Therefore, an investigation into the effects of a less severe lesion, such as the gentamicin regimen proposed here which preserves spontaneous neuronal activity, would be of significant translational value.
