Poster abstracts
Poster number 87 submitted by Zach Zixu Guo
Complement C3 Depletion Reduces Noise-induced Cochlear damage and Protects Hearing by Attenuating Chronic Cochlear Inflammation
Zixu Guo (Ohio State University; Department of Otolaryngology), Mina Shenouda (Ohio State University), Angela Wang (Ohio State University), Shengyin Lin (Ohio State University; Department of Otolaryngology), Ruili Xie (Ohio State University; Department of Otolaryngology)
Abstract:
Noise-induced hearing loss (NIHL) is characterized by cochlear dysfunction and pathology, including loss of sensory hair cells and ribbon synapses. Growing evidence indicates that immune responses shape cochlear tissue damage and the clearance of damaged cells after noise injury, but the mechanisms regulating these processes remain unclear. The complement system, a key component of innate immunity, responds to tissue damage and promotes debris clearance; however, its role in the cochlea remains poorly understood. Our prior work showed that complement C3 is activated and dynamically opsonizes damaged structures within the organ of Corti in CBA/CaJ mice after 2-hour noise exposure at 112 dB SPL. However, this severe exposure produced similar NIHL in control and C3-deficient mice, likely due to a floor effect. Here, we investigated the functional impact of C3 activation and its underlying mechanisms under moderate cochlear damage induced by 106 dB SPL noise exposure.
We compared auditory and cellular outcomes between wild-type C57BL/6 mice and homozygous C3 knockout mice (C3KO). Mice were exposed to octave-band noise (8–16 kHz) at 106 dB SPL for 2 hours. Auditory brainstem response (ABR) thresholds were measured at multiple post-exposure time points to assess hearing function. Cochleae were harvested for whole-mount immunohistochemistry using markers for sensory hair cells, ribbon synapses, and macrophages to evaluate cellular pathology, cochlear inflammation, and potential mechanisms linking C3 activation to NIHL.
C3KO mice showed similar acute cochlear damage and hearing loss compared with wild-type mice within 2 weeks after noise exposure. However, at later time points, progressive loss of outer hair cells and ribbon synapses, as well as hearing loss, were attenuated in C3KO mice. These protective effects were accompanied by reduced macrophage density and activation, suggesting that C3 activity contributes to chronic cochlear inflammation and exacerbates noise-induced pathology.
Together, our findings demonstrate that complement C3 contributes to long-term cochlear damage and inflammation after noise injury. Targeting C3 or its downstream signaling pathways may provide long-term protection against inflammation-driven progressive hearing loss.
Keywords: Noise-induced Hearing Loss, Complement System