The tectorial membrane has a critical role in metabolic age-related hearing loss.

Abstract

BACKGROUND: Millions of older adults have age-related hearing loss (ARHL), a disorder where potassium-secreting cells in the cochlea's lateral wall often degenerate. The degeneration reduces the force that drives ions into the sensory cells during sound stimulation, which is traditionally thought to explain the loss of hearing. Here we describe previously unknown mechanisms underlying this metabolic form of ARHL. METHODS: Fluorescence spectroscopy and live-cell imaging was used in Dunkin-Hartley guinea pigs of either sex to investigate the effects of lateral wall dysfunction on the hearing organ and its accessory structures. Critical findings were confirmed by studying samples of human temporal bones. FINDINGS: Lateral wall dysfunction caused calcium levels in the inner ear to decline, a change that was most pronounced in the tectorial membrane, an accessory structure crucial for transmitting acoustic stimuli to sensory cell stereocilia. This calcium depletion deprived the sensory cells of an essential ion. Additionally, the tectorial membrane detached from stereocilia, significantly impairing their ability to respond to sound. Sound-evoked responses were further decreased by sustained contraction of the entire hearing organ. INTERPRETATION: These findings establish the tectorial membrane as a key factor in metabolic ARHL, which needs to be considered when developing better diagnostic tools or treatments. FUNDING: Swedish Research Council grants 2017-06092 and 2022-00548, Swedish Brain foundation grant FO2023-0171 and US National Institutes of Health grant R01DC000141-44.