Chinchilla models of selective cochlear hair cell loss

McFadden, Sandra L.; Ding, Dalian; Jiang, Haiyan; Woo, Jenifer M; Salvi, Richard

doi:10.1016/s0378-5955(02)00697-4

Cited by 31 publications

(26 citation statements)

References 44 publications

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“…Furthermore, while dye entry into cochlear hair cells was enhanced, entry into vestibular hair cells was not, a pattern of dye distribution that mirrors the pattern of hair cell loss. The bumetanide-kanamycin combination produced extensive death of cochlear hair cells, but the vestibular organs were completely unaffected, a differential sensitivity to a diuretic-aminoglycoside combination also found in chinchillas (McFadden et al 2002). Thus, the dye appears to be a tracer for the distribution of the damaging agent.…”

Section: Discussionmentioning

confidence: 96%

Rapid Hair Cell Loss: A Mouse Model for Cochlear Lesions

Taylor

Nevill

Forge

2007

JARO

145

131

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In comparison to other mammals, mice have proved extremely resistant to aminoglycoside-induced hair cell ablation in vivo. In this paper we examine the pattern and extent of cochlear lesions rapidly induced with a combination of a single dose of aminoglycoside (kanamycin) followed by a loop diuretic (bumetanide). With this protocol, the vestibular system was unaffected, but in the cochlea, there was extensive loss of outer hair cells (OHC) that commenced in the basal coil and progressed apically so that, by 48 h, OHC loss was almost complete. TUNEL-positive nuclei and activated caspase-3 labeling demonstrated that most OHC died via a classical apoptotic pathway. However, scattered debris within the OHC region suggested that many apoptotic cells ruptured prior to completion of apoptosis. Following lesion repair, supporting cells retained characteristics of differentiated cells but positional shift occurred. In comparison to OHC loss, inner hair cell (IHC) death was delayed and only observed in 50% of all cochleae examined even after extensive reorganization of the tissue. The coadmininstration of diuretic with FM1-43, used as a tracer for aminoglycoside uptake, indicated entry into IHC as readily as OHC, suggesting that the differential response to aminoglycoside was not due to differential uptake. Where IHC death was ongoing, there were indications of different modes of cell death: cells with morphological features of autophagy, necrosis, and apoptosis were apparent. In addition to damage to the organ of Corti, there was a significant and progressive decrease in strial thickness beginning as early as 7 days posttreatment. This was due predominantly to degeneration of marginal cells. The strial pathology resembled that reported after noise damage and with aging. This in vivo protocol provides a robust model in which to obtain extensive OHC loss in the mature cochleae of mice and is a means with which to examine different aspects of cochlear pathology in transgenic or mutant strains.

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Section: Discussionmentioning

confidence: 96%

Rapid Hair Cell Loss: A Mouse Model for Cochlear Lesions

Taylor

Nevill

Forge

2007

JARO

145

131

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“…In chinchillas and other species, OHC dysfunction or loss reduces hearing sensitivity and tuning (Cody and Russell 1985;Borg 1987;Davis et al 1989;Hamernik et al 1989;McFadden et al 2002;Davis et al 2005). Not all reports, however, attribute poorer tuning to OHC loss (Nienhuys and Clark 1979;Prosen et al 1989).…”

Section: Introductionmentioning

confidence: 99%

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss

Lobariñas

Salvi

Ding

2015

JARO

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Poorer hearing in the presence of background noise is a significant problem for the hearing impaired. Ototoxic drugs, ageing, and noise exposure can damage the sensory hair cells of the inner ear that are essential for normal hearing sensitivity. The relationship between outer hair cell (OHC) loss and progressively poorer hearing sensitivity in quiet or in competing background noise is supported by a number of human and animal studies. In contrast, the effect of moderate inner hair cell (IHC) loss or dysfunction shows almost no impact on behavioral measures of hearing sensitivity in quiet, when OHCs remain intact, but the relationship between selective IHC loss and hearing in noise remains relatively unknown. Here, a moderately high dose of carboplatin (75 mg/kg) that produced IHC loss in chinchillas ranging from 40 to 80 % had little effect on thresholds in quiet. However, when tested in the presence of competing broadband (BBN) or narrowband noise (NBN), thresholds increased significantly. IHC loss 960 % increased signal-to-noise ratios (SNRs) for tones (500-11,300 Hz) in competing BBN by 5-10 dB and broadened the masking function under NBN. These data suggest that IHC loss or dysfunction may play a significant role in listening in noise independent of OHC integrity and that these deficits may be present even when thresholds in quiet are within normal limits.

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“…Animal models can play important roles in auditory research, particularly research aimed at improving cochlear prostheses, understanding central auditory plasticity, and developing strategies for inner ear rescue and repair (McFadden et al, 2002). Gene therapy in the inner ear is applied in animal models of ototoxicity and ischemiareperfusion injury (Maiorana and Staecker, 2005).…”

Section: Animal Models For Inner Ear Gene Therapymentioning

confidence: 99%

Current Status and Prospects of Gene Therapy for the Inner Ear

2011

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Inner ear diseases are common and often result in hearing disability. Sensorineural hearing loss is the main cause of hearing disability. So far, no effective treatment is available although some patients may benefit from a hearing aid equipped with a hearing amplifier or from cochlear implantation. Inner ear gene therapy has become an emerging field of study for the treatment of hearing disability. Numerous new discoveries and tremendous advances have been made in inner ear gene therapy including gene vectors, routes of administration, and therapeutic genes and targets. Gene therapy may become a treatment option for inner ear diseases in the near future. In this review, we summarize the current state of inner ear gene therapy including gene vectors, delivery routes, and therapeutic genes and targets by examining and analyzing publications on inner ear gene therapy from the literature and patent documents, and identify promising patents, novel techniques, and vital research projects. We also discuss the progress and prospects of inner ear gene therapy, the advances and shortcomings, with possible solutions in this field of research.

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Chinchilla models of selective cochlear hair cell loss

Cited by 31 publications

References 44 publications

Rapid Hair Cell Loss: A Mouse Model for Cochlear Lesions

Rapid Hair Cell Loss: A Mouse Model for Cochlear Lesions

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss

Current Status and Prospects of Gene Therapy for the Inner Ear

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