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Cited by 134Hearing, Cochlea, Tinnitus, GeneticsVestibular and auditory disordersHearing Loss and Rehabilitation

Inflammatory and immune responses in the cochlea: potential therapeutic targets for sensorineural hearing loss

Open access
Fujioka, Masato, Okano, Hideyuki, Ogawa, Kaoru·2014·Frontiers in Pharmacology
DOI 10.3389/fphar.2014.00287PMC PMC4274906
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Abstract

The inner ear was previously assumed to be an "immune-privileged" organ due to the existence of its tight junction-based blood-labyrinth barrier. However, studies performed during the past decade revealed that the mesenchymal region of the cochlea, including its lateral wall, is a common site of inflammation. Neutrophils do not enter this region, which is consistent with the old dogma; however, bone marrow-derived resident macrophages are always present in the spiral ligament of the lateral wall and are activated in response to various types of insults, including noise exposure, ischemia, mitochondrial damage, and surgical stress. Recent studies have also revealed another type of immune cell, called perivascular melanocyte-like macrophages (PVM/Ms), in the stria vascularis. These dedicated antigen-presenting cells also control vascular contraction and permeability. This review discusses a series of reports regarding inflammatory/immune cells in the cochlear lateral wall, the pathways involved in cochlear damage and their potential as therapeutic targets.

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  • There are lower risks of immunogenicity when targeting AAV vectors towards relatively immune-privileged sites, such as the subretinal space and the cochlea.

    “Additionally, there are lower risks of immunogenicity when targeting AAV vectors towards relatively immune-privileged sites, such as the subretinal space and the cochlea [93,94].”

    From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [94]

    The Introduction (page not supplied) says the cochlea was assumed to be immune-privileged, like the eye, because of its blood-labyrinth barrier. The paper also says this view has been challenged by evidence of cochlear inflammation. It does not address AAV vectors, subretinal delivery, or whether targeting either site lowers immunogenicity risk. (LLM, conf=0.82)

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Research works printed but not linked: 33

  1. Berti R. Williams A. J. Moffett J. R. Hale S. L. Velarde L. C. Elliott P. J. (2002). Quantitative real-time RT-PCR analysis of inflammatory gene expression associated with ischemia-reperfusion brain injury. J. Cereb. Blood Flow Metab. 22 1068– 1079 10.1097/00004647-200209000-00004 12218412 · DOI
  2. Cuadros M. A. Navascues J. (1998). The origin and differentiation of microglial cells during development. Prog. Neurobiol. 56 173– 189 10.1016/S0301-0082(98)00035-5 9760700 · DOI
  3. Dai M. Shi X. (2011). Fibro-vascular coupling in the control of cochlear blood flow. PLoS ONE 6: e20652 10.1371/journal.pone.0020652 PMC3106013 21673815 · DOI
  4. Fredelius L. Johansson B. Bagger-Sjoback D. Wersall J. (1990). Time-related changes in the guinea pig cochlea after acoustic overstimulation. Ann. Otol. Rhinol. Laryngol. 99 369– 378 10.1177/000348949009900510 2337316 · DOI
  5. Fredelius L. Rask-Andersen H. (1990). The role of macrophages in the disposal of degeneration products within the organ of corti after acoustic overstimulation. Acta Otolaryngol. 109 76– 82 10.3109/00016489009107417 2309562 · DOI
  6. Fujioka M. Kanzaki S. Okano H. J. Masuda M. Ogawa K. Okano H. (2006). Proinflammatory cytokines expression in noise-induced damaged cochlea. J. Neurosci. Res. 83 575– 583 10.1002/jnr.20764 16429448 · DOI
  7. Fujioka M. Okamoto Y. Shinden S. Okano H. J. Okano H. Ogawa K. (2014). Pharmacological inhibition of cochlear mitochondrial respiratory chain induces secondary inflammation in the lateral wall: a potential therapeutic target for sensorineural hearing loss. PLoS ONE 9: e90089 10.1371/journal.pone.0090089 PMC3948682 24614528 · DOI
  8. Gratton M. A. Eleftheriadou A. Garcia J. Verduzco E. Martin G. K. Lonsbury-Martin B. L. (2011). Noise-induced changes in gene expression in the cochleae of mice differing in their susceptibility to noise damage. Hear. Res. 277 211– 226 10.1016/j.heares.2010.12.014 21187137 PMC3098916 · DOI
  9. Guinan J. J. Jr. Salt A. Cheatham M. A. (2012). Progress in cochlear physiology after Bekesy. Hear. Res. 293 12– 20 10.1016/j.heares.2012.05.005 22633944 PMC3530189 · DOI
  10. Harris J. P. (1983). Immunology of the inner ear: response of the inner ear to antigen challenge. Otolaryngol. Head Neck Surg. 91 18– 32. 6405344
  11. Harris J. P. (1984). Immunology of the inner ear: evidence of local antibody production. Ann. Otol. Rhinol. Laryngol. 93 157– 162 10.1177/000348948409300211 6712089 · DOI
  12. Harris J. P. Low N. C. House W. F. (1985). Contralateral hearing loss following inner ear injury: sympathetic cochleolabyrinthitis? Am. J. Otol. 6 371– 377. 4050980
  13. Hashimoto S. Billings P. Harris J. P. Firestein G. S. Keithley E. M. (2005). Innate immunity contributes to cochlear adaptive immune responses. Audiol. Neurootol. 10 35– 43 10.1159/000082306 15567913 · DOI
  14. Hess D. C. Abe T. Hill W. D. Studdard A. M. Carothers J. Masuya M. (2004). Hematopoietic origin of microglial and perivascular cells in brain. Exp. Neurol. 186 134– 144 10.1016/j.expneurol.2003.11.005 15026252 · DOI
  15. Hibino H. Kurachi Y. (2006). Molecular and physiological bases of the K+ circulation in the mammalian inner ear. Physiology (Bethesda) 21 336– 345 10.1152/physiol.00023.2006 16990454 · DOI
  16. Hirose K. Discolo C. M. Keasler J. R. Ransohoff R. (2005). Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma. J. Comp. Neurol. 489 180– 194 10.1002/cne.20619 15983998 · DOI
  17. Hirose K. Liberman M. C. (2003). Lateral wall histopathology and endocochlear potential in the noise-damaged mouse cochlea. J. Assoc. Res. Otolaryngol. 4 339– 352 10.1007/s10162-002-3036-4 14690052 PMC1805786 · DOI
  18. Hoya N. Okamoto Y. Kamiya K. Fujii M. Matsunaga T. (2004). A novel animal model of acute cochlear mitochondrial dysfunction. Neuroreport 15 1597– 1600 10.1097/01.wnr.0000133226.94662.80 15232290 · DOI
  19. Hu X. Leak R. K. Shi Y. Suenaga J. Gao Y. Zheng P. (2014). Microglial and macrophage polarization-new prospects for brain repair. Nat. Rev. Neurol. 10.1038/nrneurol.2014.207 [Epub ahead of print]. PMC4395497 25385337 · DOI
  20. Jabba S. V. Oelke A. Singh R. Maganti R. J. Fleming S. Wall S. M. (2006). Macrophage invasion contributes to degeneration of stria vascularis in Pendred syndrome mouse model. BMC Med. 4: 37 10.1186/1741-7015-4-37 PMC1796619 17187680 · DOI
  21. Lang H. Ebihara Y. Schmiedt R. A. Minamiguchi H. Zhou D. Smythe N. (2006). Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear: mesenchymal cells and fibrocytes. J. Comp. Neurol. 496 187– 201 10.1002/cne.20929 16538683 PMC2561311 · DOI
  22. LeMasurier M. Gillespie P. G. (2005). Hair-cell mechanotransduction and cochlear amplification. Neuron 48 403– 415 10.1016/j.neuron.2005.10.017 16269359 · DOI
  23. Masuda M. Yamazaki K. Kanzaki J. Hosoda Y. (1994). Ultrastructure of melanocytes in the dark cell area of human vestibular organs: functional implications of gap junctions, isolated cilia, and annulate lamellae. Anat. Rec. 240 481– 491 10.1002/ar.1092400406 7879900 · DOI
  24. McCabe B. F. (1989). Autoimmune inner ear disease: therapy. Am. J. Otol. 10 196– 197 10.1001/2013.jamaoto.76 2750868 · DOI
  25. Nishimoto N. Kishimoto T. (2006). Interleukin 6: from bench to bedside. Nat. Clin. Pract. Rheumatol. 2 619– 626 10.1038/ncprheum0338 17075601 · DOI
  26. Okamoto Y. Hoya N. Kamiya K. Fujii M. Ogawa K. Matsunaga T. (2005). Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea. Audiol. Neurootol. 10 220– 233 10.1159/000084843 15809501 · DOI
  27. Okano T. Nakagawa T. Kita T. Kada S. Yoshimoto M. Nakahata T. (2008). Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea. J. Neurosci. Res. 86 1758– 1767 10.1002/jnr.21625 18253944 · DOI
  28. Satoh H. Firestein G. S. Billings P. B. Harris J. P. Keithley E. M. (2003). Proinflammatory cytokine expression in the endolymphatic sac during inner ear inflammation. J. Assoc. Res. Otolaryngol. 4 139– 147 10.1007/s10162-002-3025-7 12943369 PMC3202716 · DOI
  29. Shi X. (2010). Resident macrophages in the cochlear blood-labyrinth barrier and their renewal via migration of bone-marrow-derived cells. Cell Tissue Res. 342 21– 30 10.1007/s00441-010-1040-2 20838812 · DOI
  30. Solares C. A. Edling A. E. Johnson J. M. Baek M.-J. Hirose K. Hughes G. B. (2004). Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides. J. Clin. Invest. 113 1210– 1217 10.1172/jci200418195 15085200 PMC385394 · DOI
  31. Wakabayashi K. Fujioka M. Kanzaki S. Okano H. J. Shibata S. Yamashita D. (2010). Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea. Neurosci. Res. 66 345– 352 10.1016/j.neures.2009.12.008 20026135 · DOI
  32. Wang Y. Hirose K. Liberman M. C. (2002). Dynamics of noise-induced cellular injury and repair in the mouse cochlea. J. Assoc. Res. Otolaryngol. 3 248– 268 10.1007/s101620020028 12382101 PMC3202415 · DOI
  33. Willrich M. A. Murray D. L. Snyder M. R. (2014). Tumor necrosis factor inhibitors: clinical utility in autoimmune diseases. Transl. Res. 10.1016/j.trsl.2014.09.006 [Epub ahead of print]. 25305470 · DOI

Cited by

Sorted by citations

Authors
Fujioka, M., Okano, H., & Ogawa, K.
Affiliations
Keio University (JP)
Corresponding author
Fujioka, Masato
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2014-12-23
Volume
5
Pages
287-287
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2014.00287
PMC
PMC4274906
OpenAlex
W1993979020
Cited by
134
References
1
Citations by year
2026: 15 · 2025: 15 · 2024: 9 · 2023: 11 · 2022: 14 · 2021: 17 · 2020: 9 · 2019: 19 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 3
FWCI
0.86
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Takeda Science Foundation (24592560)
  • Ministry of Education, Culture, Sports, Science and Technology (24592560)
  • Ministry of Health, Labour and Welfare
  • Japan Society for the Promotion of Science (26670748, 24592560)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
  • Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Hearing Loss and Rehabilitation
Keywords
sensorineural hearing loss, cochlear inflammation, cochlear lateral wall, stria vascularis, immune privilege, blood-labyrinth barrier, noise-induced hearing loss, cochlear ischemia, mitochondrial damage, therapeutic target

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