Navigating Hereditary Hearing Loss: Pathology of the Inner Ear

Abstract

Inherited forms of deafness account for a sizable portion of hearing loss among children and adult populations. Many patients with sensorineural deficits have pathological manifestations in the peripheral auditory system, the inner ear. Within the hearing organ, the cochlea, most of the genetic forms of hearing loss involve defects in sensory detection and to some extent, signaling to the brain via the auditory cranial nerve. This review focuses on peripheral forms of hereditary hearing loss and how these impairments can be studied in diverse animal models or patient-derived cells with the ultimate goal of using the knowledge gained to understand the underlying biology and treat hearing loss.

Keywords: afferent neurons; cochlea; endolymph; hair cells; organ of corti; stria vascularis.

FIGURE 1

Left panel, schematic of a cross sectional view of the cochlea, the hearing organ of the inner ear. The three regions of interest for this review are indicated. The fluid-filled middle compartment (scala media) contains the stria vascularis, a multilayer of cells (green) that generates the high concentration of potassium ions that are needed for sound detection. The neuroepithelium (organ of Corti) is comprised of sensory hair cells (inner and outer hair cells indicated in blue) embedded in a layer of supporting cells. Auditory hair cells are innervated by afferent or spiral ganglion neurons (yellow) that project to the hindbrain. Middle panel indicates the animal and cell models (Mus Musculus mice, Danio rerio zebrafish larvae, Drosophila flies, and human-derived cells) used for the studies of pathology induced by mutations in the orthologs of four different examples of human deafness genes (right panel). For a more comprehensive list of deafness genes please see the Hereditary Hearing Loss web site (https://hereditaryhearingloss.org/). A brief summary of the findings is included. EP, endocochlear potential; TMC, transmembrane channel-like; MET, mechanotransduction.