Semin Hear 2003; 24(2): 093-098
DOI: 10.1055/s-2003-39835
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

New Frontiers in the Amelioration of Hearing Loss: Part 2-Hair Cell Development, Regeneration, Protection, and Rescue

Dwayne D. Simmons
  • Central Institute for the Deaf, Departments of Otolaryngology, Anatomy, and Neurobiology, Washington University School of Medicine, St. Louis, Missouri
Further Information

Publication History

Publication Date:
11 June 2003 (online)

The focus of the Central Institute for the Deaf conference (New Frontiers in the Amelioration of Hearing Loss, St. Louis, MO, March 22-25, 2001) was on the amelioration of hearing loss. In recent years, there has been an explosion of information on the fundamental biology of the auditory system. This explosion has paralleled significant advances in sensory aids as well as our understanding of auditory processing and rehabilitation. The overall objective of this conference was to bring together basic scientists who study cellular and molecular mechanisms of sensory cells with clinical scientists and engineers who work on the characteristics and development of sensory aids and treatments. We have published the proceedings of this conference in two issues. Part 1 (Seminars in Hearing, volume 23, number 1, 2002) was on issues related to new ideas in aural rehabilitation and sensory aids. Part 2 (this issue) focuses on hair cell development, regeneration, protection, and rescue.

As we increase our knowledge of the biology of sensory cells, it calls to question what, if any, potential applications to the treatment of hearing loss are possible. A multifaceted approach that includes biochemical, cellular, physiological, and behavioral investigations is necessary to understand the complex processes that underlie restoration of auditory function. At the biological level, most of the work related to the amelioration of hearing loss centers around sensory cell regeneration and development and around sensory cell protection and rescue. The realization of clinical gains from this research will require years of sustained investigation, but the potential benefits are great. Sensorineural hearing loss has long been considered irreversible because the production of hair cells and nerve cells in the inner ear normally ceases before birth. However, animal research has shown that under certain conditions, hair cell production can be reactivated in mature damaged ears. It also is known that these regenerated cells contribute to a recovery of hearing. Understanding the mechanisms of development is important in several ways: in regenerated sensory systems in which function is predicated on connecting neurons with regenerated sensory cells and in cochlear implants that depend on surviving neurons for their prosthetic efficacy. The mechanisms underlying these processes could be applied to enhance the efficacy of the restoration of auditory function. Research on the molecular control and cellular mechanisms of this self-repair process has been possible with modern biological methods. Although major inroads have been made in understanding the conditions under which exposure to noise or ototoxic agents cause hearing loss, the elucidation of the molecular mechanisms leading to the impairment of auditory function remains unresolved. Knowledge of these mechanisms will enable the design of rational approaches to prevention, amelioration, and treatment, which are the major concerns in research on these auditory disorders. Elucidation of these basic processes should lead to future therapeutic advances.

REFERENCES

  • 1 Cotanche D A, Saunders J C, Tilney L G. Hair cell damage produced by acoustic trauma in the chick cochlea.  Hear Res . 1987;  25 267-286
  • 2 Cruz R M, Lambert P R, Rubel E W. Light microscopic evidence of hair cell regeneration after gentamicin toxicity in chick cochlea.  Arch Otolaryngol Head Neck Surg . 1987;  113 1058-1062
  • 3 Jorgensen J M, Mathiesen C. The avian inner ear. Continuous production of hair cells in vestibular sensory organs, but not in the auditory papilla.  Naturwissenschaften . 1988;  75 319-320
  • 4 Corwin J T, Cotanche D A. Regeneration of sensory hair cells after acoustic trauma.  Science . 1988;  240 1772-1774
  • 5 Warchol M E, Lambert P R, Goldstein B J, Forge A, Corwin J T. Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans.  Science . 1993;  259 1619-1622
  • 6 Forge A, Li L, Corwin J T, Nevill G. Ultrastructural evidence for hair cell regeneration in the mammalian inner ear.  Science . 1993;  259 1616-1619
  • 7 Rubel E W, Dew L A, Roberson D W. Mammalian vestibular hair cell regeneration.  Science . 1995;  267 701-707
  • 8 Zheng W, Knudsen E I. Functional selection of adaptive auditory space map by GABAA-mediated inhibition.  Science . 1999;  284 962-995
  • 9 Corwin J T, Warchol M E. Auditory hair cells: structure, function, development, and regeneration.  Annu Rev Neurosci . 1991;  14 301-333
  • 10 Corwin J T, Warchol M E, Kelley M W. Hair cell development.  Curr Opin Neurobiol . 1993;  3 32
  • 11 Stone J S, Oesterle E C, Rubel E W. Recent insights into regeneration of auditory and vestibular hair cells.  Curr Opin Neurol . 1998;  11 17-24
  • 12 Staecker H, Van De Water R T. Factors controlling hair-cell regeneration/repair in the inner ear.  Curr Opin Cell Biol . 1998;  8 480-487
  • 13 Ryals B M, Rubel E W. Hair cell regeneration after acoustic trauma in adult Coturnix quail.  Science . 1988;  240 1774-1776
  • 14 Girod D A, Duckert L G, Rubel E W. Possible precursors of regenerated hair cells in the avian cochlea following acoustic trauma.  Hear Res . 1989;  42 175-194
  • 15 Yan H, Schlessinger J, Chao M V. Chimeric NGF-EGF receptors define domains responsible for neuronal differentiation.  Science . 1991;  252 561-563
  • 16 Lippe W R, Westbrook E W, Ryals B M. Hair cell regeneration in the chicken cochlea following aminoglycoside toxicity.  Hear Res . 1991;  56 203-210
  • 17 Hashino E, Tanaka Y, Sokabe M. Hair cell damage and recovery following chronic application of kanamycin in the chick cochlea.  Hear Res . 1991;  52 356-368
  • 18 Roberson D F, Weisleder P, Bohrer P S, Rubel E W. Ongoing production of sensory cells in the vestibular epithelium of the chick.  Hear Res . 1992;  57 166-174
  • 19 Cotanche D A, Lee K H, Stone J S, Picard D A. Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage.  Anat Embryol (Berl) . 1994;  189 1-18
  • 20 Zheng X Y, Salvi R J, McFadden S L, Ding D L, Henderson D. Recovery of kainic acid excitotoxicity in chinchilla cochlea.  Ann N Y Acad Sci . 1999;  884 255-269
  • 21 Jones J E, Corwin J T. Regeneration of sensory cells after laser ablation in the lateral line system: hair cell lineage and macrophage behavior revealed by time-lapse video microscopy.  J Neurosci . 1996;  16 649-662
  • 22 Raphael Y, Athey B D, Wang Y, Hawkins J EJ. Structure of the reticular lamina and repair after noise injury.  Rev Laryngol Otol Rhinol (Bord) . 1993;  114 171-175
  • 23 Tsue T T, Oesterle E C, Rubel E W. Hair cell regeneration in the inner ear.  Otolaryngol Head Neck Surg . 1994;  111 281-301
  • 24 Stone J S, Cotanche D A. Identification of the timing of S phase and the patterns of cell proliferation during hair cell regeneration in the chick cochlea.  J Comp Neurol . 1994;  341 50-67
  • 25 Warchol M E, Corwin J T. Regenerative proliferation in organ cultures of the avian cochlea: identification of the initial progenitors and determination of the latency of the proliferative response.  J Neurosci . 1996;  16 5466-5477
  • 26 Gleich O, Dooling R J, Presson J C. Evidence for supporting cell proliferation and hair cell differentiation in the basilar papilla of adult Belgian Waterslager canaries (Serinus canarius).  J Comp Neurol . 1997;  377 5-14
  • 27 Stone J S, Leano S G, Baker L P, Rubel E W. Hair cell differentiation in chick cochlear epithelium after aminoglycoside toxicity: in vivo and in vitro observations.  J Neurosci . 1996;  16 6157-6174
  • 28 Stone J S, Rubel E W. Cellular studies of auditory hair cell regeneration in birds.  Proc Natl Acad Sci U S A . 2000;  97 11714-11721
  • 29 Baird R A, Steyger P S, Schuff N R. Mitotic and nonmitotic hair cell regeneration in the bullfrog vestibular otolith organs.  Ann N Y Acad Sci . 1996;  781 59-70
  • 30 Li L, Forge A. Morphological evidence for supporting cell to hair cell conversion in the mammalian utricular macula.  Int J Dev Neurosci . 1997;  15 433-446
  • 31 Adler H J, Raphael Y. New hair cells arise from supporting cell conversion in the acoustically damaged chick inner ear.  Neurosci Lett . 1996;  205 17-20
  • 32 Adler H J, Komeda M, Raphael Y. Further evidence for supporting cell conversion in the damaged avian basilar papilla.  Int J Dev Neurosci . 1997;  15 375-385
  • 33 Fritzsch B, Silos-Santiago I I, Bianchi L M, Farinas I I. Effects of neurotrophin and neurotrophin receptor disruption on the afferent inner ear innervation.  Semin Cell Dev Biol . 1997;  8 277-284
  • 34 Frank T C, Dye B J, Newlands S D, Dickman J D. Streptomycin ototoxicity and hair cell regeneration in the adult pigeon utricle.  Laryngoscope . 1999;  109 356-361
  • 35 Dye B J, Frank T C, Newland S D, Dickman J D. Distribution and time course of hair cell regeneration in the pigeon utricle.  Hear Res . 1999;  133 17-26
  • 36 Simmons D D, Mansdorf N B, Kim J H. Olivocochlear innervation of inner and outer hair cells during postnatal maturation: evidence for a waiting period.  J Comp Neurol . 1996;  370 551-562
  • 37 Simmons D D, Morley B J. Differential expression of the alpha 9 nicotinic acetylcholine receptor subunit in neonatal and adult cochlear hair cells.  Brain Res Mol Brain Res . 1998;  56 287-292
  • 38 Morley B J, Simmons D D. Developmental mRNA expression of the alpha-10 nicotinic acetylcholine receptor subunit in the rat cochlea (in press).  Dev Brain Res 2002.
  • 39 Luo L, Bennett T, Jung H H, Ryan A F. Developmental expression of alpha 9 acetylcholine receptor mRNA in the rat cochlea and vestibular inner ear.  J Comp Neurol . 1998;  393 320-331
  • 40 Zuo J, Treadaway J, Buckner T W, Fritzsch B. Visualization of alpha9 acetylcholine receptor expression in hair cells of transgenic mice containing a modified bacterial artificial chromosome.  Proc Natl Acad Sci U S A . 1999;  96 14100-14105
  • 41 Subramaniam M, Campo P, Henderson D. Development of resistance to hearing loss from high frequency noise.  Hear Res . 1991;  56 65-68
  • 42 Canlon B, Ryan A F, Boettcher F A. On the factors required for obtaining protection against noise trauma by prior acoustic experience.  Hear Res . 1999;  127 158-161
  • 43 Altschuler R A, Fairfield D, Cho Y. Stress pathways in the rat cochlea and potential for protection from acquired deafness.  Audiol Neurootol . 2002;  7 152-156
  • 44 Liberman M C, Dodds L W. Single-neuron labeling and chronic cochlear pathology. II. Stereocilia damage and alterations of spontaneous discharge rates.  Hear Res . 1984;  16 43-53
  • 45 Yoshida N, Liberman M C, Brown M C, Sewell W F. Gentamicin blocks both fast and slow effects of olivocochlear activation in anesthetized guinea pigs.  J Neurophysiol . 1999;  82 3168-3174
  • 46 Mills J H, Boettcher F A, Dubno J R. Interaction of noise-induced permanent threshold shift and age-related threshold shift.  J Acoust Soc Am . 1997;  101 1681-1686
  • 47 Fessenden J D, Schacht J. The nitric oxide/cyclic GMP pathway: a potential major regulator of cochlear physiology.  Hear Res . 1998;  118 168-176
  • 48 Ohlemiller K K, McFadden S L, Ding D L. Targeted deletion of the cytosolic Cu/Zn-superoxide dismutase gene (Sod1) increases susceptibility to noise-induced hearing loss.  Audiol Neurootol . 1999;  4 237-246
  • 49 Forge A, Schacht J. Aminoglycoside antibiotics.  Audiol Neurootol . 2000;  5 3-22
  • 50 Saunders S S, Salvi R J. Pure tone masking patterns in adult chickens before and after recovery from acoustic trauma.  J Acoust Soc Am . 1995;  98 1365-1371
  • 51 McFadden S L, Henderson D, Quaranta A. Remote masking in normal-hearing and noise-exposed chinchillas.  Audiol Neurootol . 1997;  2 128-138
  • 52 Hu B H, Zheng X Y, McFadden S L, Kopke R D, Henderson D. R-phenylisopropyladenosine attenuates noise-induced hearing loss in the chinchilla.  Hear Res . 1997;  113 198-206
  • 53 Wang Y, Newton D C, Marsden P A. Neuronal NOS: gene structure, mRNA diversity, and functional relevance.  Crit Rev Neurobiol . 1999;  13 21-43
  • 54 Ogilvie J M, Speck J D, Lett J M. Growth factors in combination, but not individually, rescue rd mouse photoreceptors in organ culture.  Exp Neurol . 2000;  161 676-685