Author(s)
Ankur Gupta, BA
Anping Xia, MD, PhD
Viktoria Schiel, MD, PhD
Ritwija Bhattacharya, PhD
Kourosh Eftekharian, MD, MPH
Peter L. Santa Maria, MBBS, PhD
Affiliation(s)
Stanford University School of Medicine;
Abstract:
Hypothesis: Deletion of CCR2 enhances outer hair cell loss through reduction of migrating macrophages in the cochlea of
mice with CSOM
Background: Chronic Suppurative Otitis Media (CSOM) is one of the most common causes of permanent hearing loss
among children in the developing world. It is characterized by chronically draining middle ear, with no effective cure.
We have shown that CSOM induces an inflammatory macrophage response in the inner ear, associated with hair cell
damage. We have also revealed that CCL-2, part of the monocyte chemoattractant protein (MCP) family, is elevated over
time following middle ear infections. MCP receptor CCR2 has been implicated in many neurodegenerative disorders. In
our current study, we investigate the role of CCR2 on hair cell damage in CSOM.
Methods: PCR genotyping was done to isolate CCR2-/-, CCR2+/-, and CCR2 +/+ mice. We inoculated Pseudomonas
bacteria to the mouse middle ear cavity for generating CSOM and monitored them at 7 and 14 days after middle ear
infection, time points before and after hair cell damage occurs in our model. We dissected the cochlea to assess hair cell
damage with whole mount specimens and evaluated macrophages within cross sections.
Results: Our results measure the OHC survival number, with Myosin VIIa immunostaining, in the cochlear basal, middle,
and apical turns at 7 and 14 days. We also measured the number of F4/80 macrophages with F4/80 immunostaining in
the cochlear turns.
Conclusions: In the future, we will continue to learn more about the mechanism in which CCR2 influences the immune
response in the inner ear and whether it plays a protective or harmful role on hair cells in CSOM.
Define Professional Practice Gap & Educational Need: Limited understanding in the inflammatory mechanism of action
in the inner ear that causes sensorineural hearing loss in CSOM.
Learning
Objectives: 1. Develop an understanding of the mechanism of inner ear inflammation in CSOM.
2. Study possible pathways that may explain the role of CCR2 on outer hair cells.
Desired
Results: Deletion of CCR2 demonstrates increased outer hair cell loss relative to CCR2 control in mice with CSOM,
showing a possible mechanism in sensorineural hearing loss due to cochlear inflammatory response.
Level of Evidence does not Apply – Basic Science Study
IRB/IACUC: Stanford APLAC 32855