scholarly journals Ectopic expression of ROR1 prevents cochlear hair cell loss in guinea pigs with noise‐induced hearing loss

2020 ◽  
Vol 24 (16) ◽  
pp. 9101-9113
Author(s):  
Jun Zhang ◽  
Wei Zhang ◽  
Qinliang Zhang
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Guinea Pigs ◽  
Ectopic Expression ◽  
Cell Loss ◽  
Noise Induced Hearing Loss ◽  
Hair Cell Loss ◽  
Cochlear Hair Cell

Neurotrophin gene therapy may be able to treat individuals with noise-induced hearing loss or neural presbyacusis

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Cell Loss ◽  
Cell Populations ◽  
Noise Induced Hearing Loss ◽  
Hair Cell Loss ◽  
Functional Impairments ◽  
Peripheral Axon

Neurotrophin (NT) cochlear gene therapy might perhaps give a single treatment that might greatly enhance neuronal survival, resulting in CI patients, provided the many challenges described above can be adequately addressed and safety concerns allayed by more animal model investigations. This is particularly crucial for juvenile CI patients, who have to rely on electrical hearing for the remainder of their lives, and whose outcomes are quite different. In addition, NT gene therapy may have the potential to treat patients with noise-induced hearing loss or neural presbyacusis (e.g., age-related cochlear synaptopathy), where primary neuronal loss is a key cause of hearing loss. Animal research into noise-induced hearing loss has shown that even exposures that generate only reversible threshold alterations and no hair cell loss can lead to permanent loss of SGN synapses on hair cells, resulting in functional impairments and ultimately SGN degeneration. Cochlear synapses frequently precede both hair cell loss and threshold increases in human ears, according to current studies. Cochlear synaptopathy is characterized by ears with intact hair cell populations and normal audiograms as "hidden" hearing loss. Many frequent perceptual abnormalities, including speech-in-noise difficulties, tinnitus, and hyperacusis, are likely produced by suppressing affected neurons, which radically alters information processing. Thus, in the future, NT gene therapy may be successful in inducing SGN peripheral axon resprouting and synaptic regeneration into residual (or even regenerated) hair cell populations. We have demonstrated compelling evidence that, in this investigation, BDNF gene therapy can boost SGN survival and enhance peripheral axon maintenance or rerouting. NT-3 has been found in adult animals exposed to acoustic damage to induce synaptic regeneration of these fibers, reconnecting them to hair cells and their ribbon synapses, and restoring hearing function. Combining BDNF and NT-3 gene therapy may be the most effective way to maintain/restore a more normal cochlear neuronal substrate.

scholarly journals Designer aminoglycosides prevent cochlear hair cell loss and hearing loss

2015 ◽  
Vol 125 (2) ◽  
pp. 583-592 ◽  
Author(s):  
Markus E. Huth ◽  
Kyu-Hee Han ◽  
Kayvon Sotoudeh ◽  
Yi-Ju Hsieh ◽  
Thomas Effertz ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Cell Loss ◽  
Hair Cell Loss ◽  
Cochlear Hair Cell

Permanent Threshold Shift and Cochlear Hair Cell Loss in the Kanamycin-Treated Guinea Pig

1978 ◽  
Vol 86 (6) ◽  
pp. ORL-886-ORL-887 ◽  
Author(s):  
Cynthia A. Prosen ◽  
Michael R. Petersen ◽  
David. B. Moody ◽  
William C. Stebbins ◽  
Joseph E. Hawkins
Keyword(s):  
Guinea Pig ◽  
Hair Cell ◽  
Hair Cells ◽  
Guinea Pigs ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Hair Cell Loss ◽  
Hearing Sensitivity ◽  
Cochlear Hair Cell ◽  
Differential Contribution

The differential contribution of the inner hair cells (IHC) and the outer hair cells (OHC) in the mammalian cochlea to hearing sensitivity was assessed in six behaviorally-trained guinea pigs by comparing audiograms preadministration and postadministration of kanamycin, an antibiotic that predominantly destroys guinea pig OHC while leaving the IHC structurally unchanged. The results support the hypothesis that only the IHC of the cochlea responds to tones approximately 50 to 60 dB above the threshold of the intact cochlea.

scholarly journals Novel oral multifunctional antioxidant prevents noise-induced hearing loss and hair cell loss

2020 ◽  
Vol 388 ◽  
pp. 107880 ◽  
Author(s):  
G.D. Chen ◽  
D.M. Daszynski ◽  
D. Ding ◽  
H. Jiang ◽  
T. Woolman ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Cell Loss ◽  
Noise Induced Hearing Loss ◽  
Hair Cell Loss

scholarly journals Noise-induced and age-related hearing loss:  new perspectives and potential therapies

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 927 ◽  
Author(s):  
M Charles Liberman
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Auditory Nerve ◽  
Cell Loss ◽  
Sensorineural Hearing ◽  
Hair Cell Loss ◽  
Age Related ◽  
Age Related Hearing Loss

The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained a “hidden hearing loss” for two reasons: 1) the neuronal cell bodies survive for years despite loss of synaptic connection with hair cells, and 2) the degeneration is selective for auditory nerve fibers with high thresholds. Although not required for threshold detection when quiet, these high-threshold fibers are critical for hearing in noisy environments. Research suggests that primary neural degeneration is an important contributor to the perceptual handicap in sensorineural hearing loss, and it may be key to the generation of tinnitus and other associated perceptual anomalies. In cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from surviving auditory neurons and re-establishment of their peripheral synapses; thus, treatments may be on the horizon.

Mechanisms of hearing loss and cell death in the cochlea of connexin mutant mice

2020 ◽  
Vol 319 (3) ◽  
pp. C569-C578
Author(s):  
Bei Chen ◽  
Hongen Xu ◽  
Yanfang Mi ◽  
Wei Jiang ◽  
Dan Guo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Hair Cell ◽  
Stria Vascularis ◽  
Reactive Oxygen Species Generation ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Spiral Ligament ◽  
Hair Cell Loss ◽  
Auditory Brain Stem Response

Mutations in connexin 30 (Cx30) are known to cause severe congenital hearing impairment; however, the mechanism by which Cx30 mediates homeostasis of endocochlear gap junctions is unclear. We used a gene deletion mouse model to explore the mechanisms of Cx30 in preventing hearing loss. Our results suggest that despite severe loss of the auditory brain-stem response and endocochlear potential at postnatal day 18, Cx30−/− mice only show sporadic loss of the outer hair cells. This inconsistency in the time course and severity of hearing and hair cell losses in Cx30−/− mice might be explained, in part, by an increase in reactive oxygen species generation beginning at postnatal day 10. The expression of oxidative stress genes was increased in Cx30−/− mice in the stria vascularis, spiral ligament, and organ of Corti. Furthermore, Cx30 deficiency caused mitochondrial dysfunction at postnatal day 18, as assessed by decreased ATP levels and decreased expression of mitochondrial complex I proteins, especially in the stria vascularis. Proteomic analysis further identified 444 proteins that were dysregulated in Cx30−/− mice, including several that are involved in mitochondria electron transport, ATP synthesis, or ion transport. Additionally, proapoptotic proteins, including Bax, Bad, and caspase-3, were upregulated at postnatal day 18, providing a molecular basis to explain the loss of hearing that occurs before hair cell loss. Therefore, our results are consistent with an environment of oxidative stress and mitochondrial damage in the cochlea of Cx30−/− mice that is coincident with hearing loss but precedes hair cell loss.

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