Bahareh Ajami, PhD, Oregon Health & Science University

The cochlea was long considered immune-privileged, but recent evidence reveals a complex landscape of resident immune cells whose roles in hearing remain poorly understood. Using cutting-edge single-cell RNA sequencing, fate-mapping, and functional approaches, we have identified five distinct myeloid cell populations in the mouse cochlea, including three macrophage subsets conserved in humans. Our comprehensive analysis reveals that these populations have diverse developmental origins—some derived from yolk sac precursors during embryogenesis, others continuously replenished by circulating monocytes in specific cochlear compartments. Strikingly, each population exhibits unique transcriptional signatures and spatial distributions that correlate with specialized functions. Through selective depletion studies, we demonstrate that specific macrophage subsets are critical for inner hair cell synapse formation and hearing, while others accumulate during age-related hearing loss. This work fundamentally reframes our understanding of cochlear immunology, revealing previously unappreciated cellular diversity that may represent new therapeutic targets for hearing disorders. The findings challenge the immune privilege paradigm and establish a foundation for precision approaches to treating hearing loss.   

Wade Chien, PhD, Johns Hopkins School of Medicine

Inner ear gene therapy is a rapidly growing field of research investigation. Currently, several clinical trials are ongoing to test the safety and efficacy of inner ear gene therapy for a specific form of hereditary hearing loss. In this talk, we will discuss the progress that has been made in the field of inner ear gene therapy. We will also address several challenges that still remain in order to translate inner ear gene therapy as an effective treatment for other types of hearing loss.

Stéphane F. Maison, PhD, CCC-A, Massachusetts Eye and Ear and Harvard Medical School

This presentation will review how Hidden Hearing Loss was discovered, some of the methods used to measure it in humans, emerging strategies that may reverse or mitigate it, and the implications of such discovery for clinical practice in audiology and otology.

Tobias Moser, MD, University Medical Center Göttingen

When hearing fails, cochlear implants (CIs) provide open speech perception to most of the currently more than a million CI users. CIs bypass the defective sensory organ and stimulate the auditory nerve electrically. The major bottleneck of current CIs is the poor coding of spectral information, which results from wide current spread from each electrode contact. As light can be more conveniently confined, optical stimulation of the auditory nerve presents a promising perspective for a fundamental advance of CIs. Developing optogenetic stimulation for auditory research and future hearing restoration requires efforts toward development and characterization of appropriate channelrhodopsins, their viral gene transfer to cochlear neurons, as well as medical device engineering. The presentation will summarize the current state of the art and plans for developing gene therapy of the auditory nerve and optical CI as well as their combination for improved hearing restoration by optogenetic sound coding.

Guisheng Zhong, PhD, Shanghai Tech University School of Life Science and Technology, iHuman Institute

Hereditary hearing loss affects millions worldwide, with gene therapy emerging as a promising treatment. This seminar explores advances in precise gene delivery and expression control, focusing on AAV-based strategies. We highlight the development of the ARBITER workflow to engineer cochlear cells specific cis-regulatory elements, successfully restoring hearing in Slc26a5 mutant mice. Additionally, I discuss recent preclinical/clinical results in OTOF gene therapies and describe the challenge to treat GJB2 deafness patients, offering insights into overcoming challenges in treating genetic deafness.