Hearing Function, Degeneration, and Disease: Spotlight on the Stria Vascularis

Abstract

The stria vascularis (SV) is a highly vascularized tissue lining the lateral wall of the cochlea. The SV maintains cochlear fluid homeostasis, generating the endocochlear potential that is required for sound transduction. In addition, the SV acts as an important blood-labyrinth barrier, tightly regulating the passage of molecules from the blood into the cochlea. A healthy SV is therefore vital for hearing function. Degeneration of the SV is a leading cause of age-related hearing loss, and has been associated with several hearing disorders, including Norrie disease, Meniere's disease, Alport syndrome, Waardenburg syndrome, and Cytomegalovirus-induced hearing loss. Despite the SV's important role in hearing, there is still much that remains to be discovered, including cell-specific function within the SV, mechanisms of SV degeneration, and potential protective or regenerative therapies. In this review, we discuss recent discoveries elucidating the molecular regulatory networks of SV function, mechanisms underlying degeneration of the SV, and otoprotective strategies for preventing drug-induced SV damage. We also highlight recent clinical developments for treating SV-related hearing loss and discuss future research trajectories in the field.

Keywords: blood-labyrinth barrier; cisplatin; clinical trial; cochlear battery; regeneration; single-cell sequencing; virus.

FIGURE 1

The stria vascularis (SV) is a highly specialized and vascularized tissue lining the lateral wall of the cochlea. (A) A cross-section of the cochlea. (B) The three conventional cell layers of the SV include the marginal cell layer (MC), the intermediate cell layer, and the basal cell layer (BC). The marginal cell layer is exposed to the endolymph and the basal cell layer interacts with spiral ligament fibrocytes. The intermediate cell layer is composed of perivascular-resident macrophage-like melanocytes (PVM/M), pericytes (PC), and endothelial cells (EC). The cell layers are tightly interlocked by infoldings and projections between the basolateral membranes of marginal cells and the PVM/Ms, and the PVM/Ms and the basal cells. (C) Other cell types in the lateral wall that contribute to SV function include spindle cells (SC) and root cells (RC). Other labels: Reisner’s membrane (RM); tectorial membrane (TM); spiral ganglion (SG); inner hair cell (IHC); outer hair cells (OHC); basilar membrane (BM); spiral ligament (SL); tight junctions (TJ); endothelial basement membrane (EBM) and intrastrial space (IS). (C) adapted from Gu et al. (2020).

FIGURE 2

The cochlear battery facilitates sound detection. Sound waves deflect hair cell stereocilia, mechanically opening K+ channels and allowing potassium ions (K+) from the scala media to enter the hair cell. The subsequent depolarization of the hair cell activates voltage-gated calcium channels, which triggers a calcium influx that causes neurotransmitter to be released at the base of the hair cell. Neurotransmitter then diffuses into the nerve terminal and causes an action potential to be created in the spiral ganglion. This signal is then transmitted to the brain for auditory processing. The SV actively returns potassium ions that were used during this process to the scala media, maintaining the endocochlear potential and allowing for continuous sound detection.

FIGURE 3

Inner ear vascular network. (A) Arterial blood supply and venous drainage of the cochlear and vestibular systems. (B) Partial corrosion casts of the mouse cochlea. The capillaries of the stria vascularis run parallel along the length of the cochlea. Figure 3B image provided by M. Carraro and R.V. Harrison.