Targeting Autophagy for Otoprotection: Translating Basic Mechanisms into Clinical Strategies

Area of Science:

• Oto-neurology
• Cellular Biology
• Regenerative Medicine

Background:

• Sensorineural hearing loss (SNHL) is a leading cause of global hearing impairment, characterized by irreversible damage to cochlear sensory cells and neurons.
• The mammalian cochlea's limited regenerative capacity means cell death is a final pathway for various insults, necessitating new therapeutic strategies beyond current compensatory treatments.

Purpose of the Study:

• To review the complex, stage-specific roles of autophagy in the cochlea and its regulation in SNHL.
• To highlight the context-dependent effects of mitophagy on cell survival.
• To introduce a novel dual-phase autophagy modulation strategy for SNHL treatment.

Main Methods:

• Literature review synthesizing current evidence on autophagy regulation in the cochlea.
• Analysis of autophagy's dual roles in SNHL, including mitophagy.
• Discussion of a proposed therapeutic paradigm for SNHL.

Main Results:

• Autophagy plays dynamic and stage-specific roles in SNHL, with mitophagy having context-dependent effects on cell survival.
• A dual-phase autophagy modulation strategy is proposed: enhancing cytoprotective autophagy early and inhibiting excessive flux later.
• This approach offers a precision-targeting framework for SNHL interventions.

Conclusions:

• Current SNHL therapies are limited; mechanistic interventions are urgently needed.
• Modulating autophagy in two phases—early enhancement and later inhibition—shows promise for preventing catastrophic cell death.
• This strategy could guide novel drug development and clinical translation for SNHL, moving towards transformative treatments.