Acquired sensorineural hearing loss, oxidative stress, and microRNAs

Area of Science:

• Otolaryngology
• Molecular Biology
• Genetics

Background:

• Hearing loss is a major global disability, with age-related hearing loss being a primary contributor.
• Acquired sensorineural hearing loss encompasses various types, including noise-induced, ototoxic, and sudden onset.
• Oxidative stress is increasingly recognized as a common factor in the complex etiology of acquired hearing loss.

Purpose of the Study:

• To review the role of microRNAs (miRNAs) in oxidative stress and hypoxia related to sensorineural hearing loss.
• To explore potential therapeutic strategies targeting miRNAs for hearing loss treatment.

Main Methods:

• A comprehensive literature search was conducted across multiple databases (Ovid EMBASE, Ovid MEDLINE, Web of Science, ClinicalTrials.gov) from August 2018 to July 2023.
• Keywords included "hearing loss," "hypoxamiRs," "hypoxia," "microRNAs," "ischemia," and "oxidative stress."
• The review synthesized findings from 11 primary journal articles and 8 registered clinical trials.

Main Results:

• Specific miRNAs, such as miR-34a and miR-29b, were found to increase with age and promote apoptosis by targeting key signaling pathways (SIRT1/PGC-1α, SIRT1/p53, SIRT1/HIF-1α).
• Hypoxia and oxidative stress induce apoptosis, which can be mitigated by resveratrol and a miR-29b inhibitor.
• Gentamicin-induced ototoxicity in mice involved reduced miR-182-5p and increased oxidative stress, an effect reversed by stem cell-derived exosomes.

Conclusions:

• MicroRNAs play a significant role in the cellular responses to hypoxia and oxidative stress, contributing to sensory hair cell death in hearing loss.
• Targeting specific miRNAs or pathways involved in oxidative stress presents a promising avenue for developing novel therapies for hearing loss.
• Further research is needed to translate these findings into effective human treatments.