The cochlear implant is considered to be the standard treatment for bilateral profound sensorineural hearing loss. However, there remains significant variability in the functional results of implantation as assessed by word recognition scores. In addition, recent evidence suggests a significant cellular immunologic response may occur in the presence of an implant in most individuals. This response may interfere with the postoperative results of implantation and also may preclude future regenerative therapy. In an effort to elucidate the cause of pathologic changes induced in the inner ear as a consequence of cochlear implantation during life, this grant submission proposes three specific aims.
Aim 1 will evaluate the preservation of cells of the organ Corti and their innervating dendritic processes following cochlear implantation in the human and build on preliminary data generated during the previous grant period. A battery of immunostains was identified which will be used in human adult specimens to determine the preservation of hair cells, supporting cells (some of which are putative progenitor cells) and neurons and will be applied to temporal bone specimens from 21 patients who in life had undergone cochlear implantation.
Aim 2 will further evaluate the immune response to the presence of a cochlear implant in the human using immunohistochemical and morphometric techniques. Specifically we will test the hypotheses that a) postoperative word recognition scores are negatively correlated with the severity of intracochlear new bone and fibrous tissue (Aim 2A); b) macrophages and microglia- like cells play a role in the cellular immune response (Aim 2B); c) the silicone carrier surrounding the cochlear electrode plays a role in the cellular inflammatory response (Aim 2C); d) finally, the fibrous capsule surrounding the implant is not symmetrically deposited which may imply that other mechanisms (such as electrical stimulation) may also be responsible for the inflammatory response.
In Aim 3, continued accrual of temporal bones from patients who in life underwent cochlear implantation is planned. It is hoped that this research will elucidate better methods of manufacture and surgery to limit the immune response to cochlear implantation and also elucidate the feasibility of applying future regenerative biologic techniques to restore hearing in patients who have already undergone cochlear implantation during life.

Public Health Relevance

The overall objective of this grant proposal is to describe, and elucidate the causes of pathologic changes within the human inner ear that occur as a consequence of cochlear implantation during life. These changes are important in that they may limit the functional result of implantation and also may limit the future use of other biologic treatments for deafness such as regeneration of the inner ear. The proposed research utilizes a rare, if not unique, resource namely a collection of inner ear specimens from 74 patients who underwent cochlear implantation during life.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC000152-34A1
Application #
9100167
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
1979-12-01
Project End
2021-02-28
Budget Start
2016-03-01
Budget End
2017-02-28
Support Year
34
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
Trakimas, Danielle R; Kozin, Elliott D; Ghanad, Iman et al. (2018) Human Otopathologic Findings in Cases of Folded Cochlear Implant Electrodes. Otol Neurotol 39:970-978
Kamakura, Takefumi; O'Malley, Jennifer T; Nadol Jr, Joseph B (2018) Preservation of Cells of the Organ of Corti and Innervating Dendritic Processes Following Cochlear Implantation in the Human: An Immunohistochemical Study. Otol Neurotol 39:284-293
O'Malley, Jennifer T; Burgess, Barbara J; Galler, Donald et al. (2017) Foreign Body Response to Silicone in Cochlear Implant Electrodes in the Human. Otol Neurotol 38:970-977
Kamakura, Takefumi; Lee, Daniel J; Herrmann, Barbara S et al. (2017) Histopathology of the Human Inner Ear in the Cogan Syndrome with Cochlear Implantation. Audiol Neurootol 22:116-123
Ishai, Reuven; Herrmann, Barbara S; Nadol Jr, Joseph B et al. (2017) The pattern and degree of capsular fibrous sheaths surrounding cochlear electrode arrays. Hear Res 348:44-53
Kamakura, Takefumi; Nadol Jr, Joseph B (2016) Correlation between word recognition score and intracochlear new bone and fibrous tissue after cochlear implantation in the human. Hear Res 339:132-41
Kamakura, Takefumi; Nadol Jr, Joseph B (2016) Cochlear Histopathology as Observed in Two Patients With a Cochlear Implant Electrode With Positioner. Otol Neurotol 37:642-6
Burgess, Barbara J; O'Malley, Jennifer T; Kamakura, Takefumi et al. (2016) Histopathology of the Human Inner Ear in the p.L114P COCH Mutation (DFNA9). Audiol Neurootol 21:88-97
Quesnel, Alicia M; Nakajima, Hideko Heidi; Rosowski, John J et al. (2016) Delayed loss of hearing after hearing preservation cochlear implantation: Human temporal bone pathology and implications for etiology. Hear Res 333:225-234
Nadol Jr, Joseph B; Handzel, Ophir; Amr, Sami (2015) Histopathology of the Human Inner Ear in a Patient With Sensorineural Hearing Loss Caused by a Variant in DFNA5. Otol Neurotol 36:1616-21

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