AOS036 - Influence of Fractalkine Receptor CX3CR1 Deletion on Cochlear Hair Cell Survival and Macrophage Expression in Chronic Suppurative Otitis Media
Saturday, April 30, 2022
10:31 AM – 10:38 AM CT
Location: Landmark A
Viktoria Schiel, MD, PhD
Anping Xia, MD, PhD
Jing Chen, MPH, DABT
Brian Bacacao, BS
Laurent A. Bekale, MD, PhD
Peter L. Santa Maria, MD, PhD
Background: Chronic Suppurative Otitis Media (CSOM) is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world.
Hypothesis: We have demonstrated that CSOM causes macrophage associated sensory hearing loss. In this report, we examined the influence of fractalkine receptor (CX3CR1) deletion (CX3CR1GFP/GFP) in CSOM.
Methods: We investigated in our novel pseudomonas aeruginosa PA CSOM animal model, previously validated to mimic the human disease.
Results: We observed partial outer hair cell (OHC) loss in the cochlear basal turn, no OHC loss in the middle and apical turns in both CX3CR1GFP/GFP and wild type (WT) mice at 14 days after bacterial inoculation. The number of OHCs in the base remained as 26.6/100 μm of the basilar membrane in CX3CR1GFP/GFP mouse and 27.0/100 μm of the basilar membrane in WT mouse. There was no significant difference (p = 0.95). In contrast to OHC loss, no IHC loss was found in all cochlear turns. We also counted F4/80 macrophages in hair cells area and outer sulcus region with Z-stack images in whole mount samples. Macrophages have 6.0/100 μm of the basilar membrane in CX3CR1GFP/GFP mice and 5.6/100 μm of the basilar membrane in WT mouse. There was also no significant difference (p = 0.68).
Conclusions: Together, the data did not support the correlation in HC loss and macrophage numbers between fractalkine receptor deletion and WT CSOM. We will further investigate the immune responses in the whole cochlea in CX3CR1GFP/GFP comparing with WT mouse.
*Professional Practice Gap & Educational Need: We propose to investigate how sensory hearing loss (SHL) is caused by chronic suppurative otitis media (CSOM): severe chronic middle ear infections. CSOM is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. It is characterized by a chronically discharging infected middle ear, and there is currently no effective cure.
*Learning Objective: To investigate the interaction between the CX3CR1 receptor function on macrophages and hair cells loss in chronic suppurative otitis media.
*Desired Result: To show a correlation between the CX3CR1 receptor function on macrophages and hair cells loss in CSOM to further investigate the immune response in sensory hearing loss.
*Level of Evidence - Level III
*Indicate IRB or IACUC: APLAC (Administrative Panel on Laboratory Animal Care, Stanford University) protocol number 32855