Perspectives on Human Hearing Loss, Cochlear Regeneration, and the Potential for Hearing Restoration Therapies

Abstract

Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of the greater problem of hearing restoration, as hearing loss can stem from a myriad of causes. This review discusses these issues and recent findings, and places them in the greater social context of need and community.

FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses

“…Deafness could be caused by genetic factors, infectious diseases, aging, ototoxic drugs, and noise exposure and is primarily attributed to the deterioration of cochlear hair cells ( Zhu et al, 2018 ; Gao et al, 2019 ; Wagner and Shin, 2019 ; Zhang Y. et al, 2019 ; Qian et al, 2020 ; Zhang et al, 2020b ; Zhou et al, 2020 ). Recently, much effort has been made to regenerate hair cells ( White, 2020 ). Although the neonatal cochlea has limited hair cell regeneration ability, this regeneration ability decreases rapidly with increased age ( Wang et al, 2015 ; Lu et al, 2017 ; He et al, 2019 ; Tan et al, 2019 ; Zhang S. et al, 2019 ; Zhang et al, 2020a , c ).…”

Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions

“…Current research mainly focuses on regeneration in the neonatal cochlea, where different types of supporting cells, including Sox2+ and Lgr5+ supporting cells, allow the opportunity for regeneration of hair cells. Whereas other reviews on the regenerative potential in the adult cochlea focus on specific pathways regulating regeneration or epigenetics [24,25], this review summarizes current knowledge and literature on regeneration in the adult cochlea through the different types of supporting cells known and their regenerative potential. Furthermore, we propose a combined strategy for regeneration, based on manipulation of key signaling pathways (e.g., Wnt, Notch, Shh, FGF, and BMP/TGFβ), manipulation of epigenetic modifications to expose transcriptional sites, and for functional effects, as well as treatments to protect and regenerate the SGNs and ribbon synapses (including neurotrophic factors, and/or TrkB receptor agonists, anti-RGMa and IGF).…”

“…In this review, we therefore summarize the development of the cochlea in mammals, necessary to understand the pathways involved in the generation of sensory hair cells and progenitors of the cochlea, as well as the presence of progenitors in the neonatal cochlea, and finally, we discuss the implications for the deafened adult mammalian cochlea. While previous reviews [24,25] mainly focused on hair cell regeneration, the current review not only evaluates the current literature on potential approaches to regenerate lost hair cells in the adult mammalian cochlea but also discusses re-innervation as that is crucial for functional improvement. For the purpose of this review, we focus on non-genetic hearing loss, considering that other treatment approaches are more likely to be effective in genetic hearing loss, in particular, gene therapy.…”