Noise-induced hearing loss: new animal models

Abstract

Purpose of the review: This article presents research findings from two invertebrate model systems with potential to advance both the understanding of noise-induced hearing loss mechanisms and the development of putative therapies to reduce human noise damage.

Recent findings: Work on sea anemone hair bundles, which resemble auditory hair cells, has revealed secretions that exhibit astonishing healing properties not only for damaged hair bundles, but also for vertebrate lateral line neuromasts. We present progress on identifying functional components of the secretions, and their mechanisms of repair. The second model, the Johnston's organ in Drosophila, is also genetically homologous to hair cells and shows noise-induced hearing loss similar to vertebrates. Drosophila offers genetic and molecular insight into noise sensitivity and pathways that can be manipulated to reduce stress and damage from noise.

Summary: Using the comparative approach is a productive avenue to understanding basic mechanisms, in this case cellular responses to noise trauma. Expanding study of these systems may accelerate identification of strategies to reduce or prevent noise damage in the human ear.

Figure 1

Anemone hair bundle anatomy and mechanotransduction. (a) The hair bundle is a multicellular complex consisting of a single sensory neuron (sn), from which projects a central kinocilium (k) and several large-diamater stereocilia (ls). Surrounding the neuron are multiple hair cells (hc) which project many small-diameter stereocilia (ss) from their apical surfaces, which connect to the large-diameter stereocilia by inter-stereociliary linkages (not shown). Modified from [6]. (b) Vibration arising from prey/probe movement (indicated by left arrow) cause deflection of linked stereocilia. This movement causes hydrodynamic shearing forces creating strain on tip-links (tl) connecting stereocilia on hair cells on the side closest to the ‘positive’ (left) direction, opening force-gated mechanotransduction channels, allowing increased cation influx (represented by open circles with ‘+’ symbols) and depolarization of the hair cell. Simultaneously, stereociliary deflection of hair cells lying on the opposite side (right) of the neuron experience a ‘negative’ deflection, slackening tip-link tension, closing mechanotransduction channels and decreasing cation influx, and hyperpolarizing the hair cell. ax – axon of sensory neuron; n – nucleus. Other abbreviations as in (a). Modified from [3].

Figure 2

Schematic overview of Drosophila scolopidium (a) and vertebrate hair cell (b) anatomy. Scolopidia consist of 2-3 sensory neurons each projecting a single sensory ciliated dendrite with biochemically and functionally distinct proximal and distal regions. The dendrites are encapsulated by scolopale and cap cells. Acoustic stimulation of the fly's antenna results in oscillatory extension/compression of scolopidia along the longitudinal axis (indicated by diagonal arrow in a), engaging the mechanotransduction apparatus to depolarize the neurons. This is functionally analogous to vertebrate hair cell depolarization by acoustically-generated forces (indicated by horizontal arrow in b) acting on stereocilia along the auditory sensory epithelium. Modified from [47].