Exosome-mediated protection of auditory hair cells from ototoxic insults

Abstract

Hearing loss caused by the death of sensory hair cells of the inner ear is an unfortunate side effect for many patients treated with aminoglycoside antibiotics or platinum-containing chemotherapy agents. In animal models, induction of heat shock confers substantial otoprotection against aminoglycoside- and cisplatin-induced hair cell death. In this issue of the JCI, Breglio et al. demonstrate that inner ear tissue released exosomes carrying heat shock protein 70 (HSP70) in response to heat stress. HSP70 acted by a paracrine mechanism that engaged the Toll-like receptor 4 (TLR4) on hair cells to protect them from death. Exosomes and the HSP70/TLR4 pathway could thus provide treatment targets for the protection of hair cells from chemically induced death or from other insults, such as noise.

Figure 1. Exosomal HSP70–mediated protection of the mammalian inner ear.

The mammalian inner ear contains the vestibule, which houses the sensory epithelia for the perception of gravity and head movements, and the cochlea, which houses the sensory epithelia for the perception of sound. Sensory epithelium from the utricle, a subcompartment of the vestibule, contains hair cells that are surrounded by supporting cells and innervated by afferent neurons. In utricle explant experiments, heat shock induced supporting cells to release exosomes containing HSP70, which bound to TLR4-expressing hair cells and protected against aminoglycoside toxicity.