Dissertation
Immune system involvement in spiral ganglion neurodegeneration after inner ear hair cell loss
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2026
DOI: 10.25820/etd.008358
Abstract
Sensorineural hearing loss, the most common form of hearing loss, is typically characterized by damage to inner ear sensory hair cells or to the spiral ganglion neurons (SGNs) that conduct auditory information from the hair cells to the brain. SGN death can occur because of direct trauma (e.g., acoustic overexposure), or secondarily after hair cell loss. Degeneration of SGNs can reduce the efficacy of cochlear implants that replace the function of hair cells by electrically stimulating SGNs. The mechanisms that promote SGN death after hair cell loss are unknown, however, mounting evidence from animal models implicates involvement of the immune response.
Administration of the aminoglycoside antibiotic kanamycin to neonatal rats results in complete loss of cochlear hair cells by 3 weeks of age and the death of more than 80% of SGNs by ~17 weeks of age. Previous studies from our lab show that after kanamycin-induced deafening, there is a significant increase in the expression of immune response related genes within the spiral ganglion, where SGNs reside, and this is accompanied by a significant increase in the abundance of immune cells.
In Chapter 2, I show that the population of immune cells responding to the ganglion after hair cell loss includes macrophages, which increase in number and activation prior to the onset of significant SGN death, and lymphocytes (T, B, and NK cells), which increase in number concomitant with SGN death. This increase in immune cell abundance and activation persists throughout the neurodegeneration period, indicating a robust and prolonged immune response occurs in the cochlea after kanamycin-induced hair cell loss. This is in contrast to what occurs during postnatal developmental pruning, where macrophages transiently increase in the ganglion, spatially and temporally correlated with SGN death, consistent with a role in clearing dying neurons. The differences between these two instances of SGN death suggest that the immune response post-deafening may have a role other than phagocytosis and instead may be causal to SGN death post-deafening. This is supported by previous studies in which elimination of macrophages or treatment with anti-inflammatory agents that reduce macrophage activation promote SGN survival after hair cell loss. However, from these results, we are unable to determine whether macrophages themselves directly contribute to SGN death, or whether they act indirectly by recruiting adaptive immune responses that are ultimately causal to SGN death.
In Chapter 3, I directly investigate the role of lymphocytes and adaptive mediated immune responses in post-deafening SGN death using two immunodeficient rat models; the T cell deficient RNU rat and the lymphocyte (T, B, and NK cell) deficient SRG rat. While lymphocytes do respond to the ganglion after hair cell loss, I show that adaptive immune responses are not causal to SGN death. Rather, regional differences in SGN survival post-deafening in the SRG rat suggest a region-specific effect of innate lymphocytes, NK cells. Together, my research implicates innate immune responses in SGN death after hair cell loss, though further investigation into the mechanisms underlying its regional variation is required.
Details
- Title: Subtitle
- Immune system involvement in spiral ganglion neurodegeneration after inner ear hair cell loss
- Creators
- Adrianna M Caro
- Contributors
- Steven H. Green (Advisor)Noah S. Butler (Committee Member)Michael E. Dailey (Committee Member)Marlan R. Hansen (Committee Member)Daniel W Summers (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Integrated Biology
- Date degree season
- Spring 2026
- DOI
- 10.25820/etd.008358
- Publisher
- University of Iowa
- Number of pages
- xi, 110 pages
- Copyright
- Copyright 2026 Adrianna M Caro
- Language
- English
- Date submitted
- 04/27/2026
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references.
- Public Abstract (ETD)
Sensorineural hearing loss (SNHL) is the most common form of hearing loss. SNHL is characterized by damage to the sensory receptors of the inner ear called hair cells, or to the neurons they connect to, called spiral ganglion neurons (SGNs). Hair cells are sensitive to damage from a wide range of causes, including aging, loud noise, and specific medications that are harmful to the inner ear. SGNs can also die from these causes either directly, or indirectly, after hair cells are lost.
When cells become damaged or die, the body responds by sending immune cells to clean up and help repair the tissue. The signals that direct these responses can become unbalanced, sometimes furthering damage instead of helping it. My research explores how the immune system interacts with SGNs after the loss of hair cell and how these interactions might contribute to SGN death.
For people with severe hearing loss, cochlear implants can help restore hearing by replacing the function of hair cells and directly stimulating SGNs. However, the effectiveness of these devices rely on surviving SGNs. My work helps further our understanding of why SGNs die after hair cell loss, helping guide the development of treatments that protect neurons and improve hearing outcomes
- Academic Unit
- Biology
- Record Identifier
- 9985177074602771
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