Author(s)
Viktoria Schiel, MD, PhD
Anping Xia, MD, PhD
Ritwija Bhattacharya, PhD
Ankur Gupta
Kourosh Eftekharian, MD
Peter Santa Maria, MD, PhD
Affiliation(s)
Stanford Otolaryngology, Head & Neck Surgery;
Abstract:
Background: CSOM is a worldwide disease that afflicts 330 million people worldwide and is the most common cause
of hearing loss in children in the developing world. We have previously found that macrophages are the main immune
cells in the cochlea mirroring the timing of hair cell loss.
Hypothesis: In this report we investigated the function of resident and migrating cochlear macrophages towards hair cell
loss in CSOM.
Methods: We investigated in our novel pseudomonas aeruginosa PA CSOM animal model, previously validated to mimic
the human disease. We depleted cochlear resident macrophages by using the CSF-1 receptor inhibitor PLX5622 before
inoculating them with PA. We determined macrophage numbers in the cochlea and hair cell loss at different timepoints
(1, 3, 7, and 14 days) during the infection course using immunohistochemistry and confocal microscopy.
Results: We found that depletion of cochlear resident macrophages did not affect hearing or cause hair cell damage in
wild type mice. This shows that resident cochlear macrophages are not required to maintain hearing. Total macrophages
were significantly reduced in the cochlea after depletion of resident macrophages at all assessed timepoints during the
infection, compared to the control group without depletion (p < 0.05). In CSOM, we did not find any hair cell loss after
1 and 3 days in both groups. However, we found hair cell loss at 7 and 14 days in both groups. We found significantly
less hair cell loss at 14 days when resident cochlear macrophages were previously depleted (p = 0.04). The number of
hair cells in the basal turn of the cochlea remained as 29/100 µm of the basilar membrane after depleting macrophages
and 19/100 µm of the basilar membrane in the control group.
Conclusions: These data suggested that both the resident and migrating macrophages play a role in CSOM associated hair
cell loss. Our further research plan will focus on the underlying molecular mechanism between macrophages and hair
cell loss.
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 role of resident and migrating macrophages towards hair cells loss in chronic
suppurative otitis media.
Desired
Results: To show the underlying mechanism between cochlear macrophages and hair cells in CSOM and identify
macrophages as a potential target for therapy to prevent sensory hearing loss in CSOM;
Level of Evidence – Level III
Indicate IRB or IACUC : APLAC (Administrative Panel on Laboratory Animal Care, Stanford University) protocol
number 32855