Molecular Pathways Modulating Sensory Hair Cell Regeneration in Adult Mammalian Cochleae: Progress and Perspectives

Noise-induced, drug-related, and age-related disabling hearing loss is a major public health problem and affect approximately 466 million people worldwide. In non-mammalian vertebrates, the death of sensory hair cells (HCs) induces the proliferation and transdifferentiation of adjacent supporting cells into new HCs; however, this capacity is lost in juvenile and adult mammalian cochleae leading to permanent hearing loss. At present, cochlear implants and hearing devices are the only available treatments and can help patients to a certain extent; however, no biological approach or FDA-approved drug is effective to treat disabling hearing loss and restore hearing. Recently, regeneration of mammalian cochlear HCs by modulating molecular pathways or transcription factors has offered some promising results, although the immaturity of the regenerated HCs remains the biggest concern. Furthermore, most of the research done is in neonates and not in adults. This review focuses on critically summarizing the studies done in adult mammalian cochleae and discusses various strategies to elucidate novel transcription factors for better therapeutics.

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Dating and relationship violence victimization and perpetration among 11–16 year olds in Wales: a cross-sectional analysis of the School Health Research Network (SHRN) survey

Journal of Public Health ◽

10.1093/pubmed/fdz084 ◽

2019 ◽

Cited By ~ 2

Author(s):

Honor Young ◽

Sara Jayne Long ◽

G J Melendez-Torres ◽

Hyun Sue Kim ◽

Gillian Hewitt ◽

...

Keyword(s):

Socioeconomic Status ◽

School Health ◽

Public Health Problem ◽

Self Report ◽

Research Network ◽

Major Public Health Problem ◽

Relationship Violence ◽

Cross Sectional ◽

Targeted Interventions ◽

Age Related

Abstract Background This study examines the prevalence of dating and relationship violence (DRV) victimization, perpetration and joint victimization and perpetration, and associations between DRV and socio-demographic characteristics. Methods Cross-sectional self-report data from 74 908 students aged 11–16 from 193 schools across Wales were collected and analysed using generalized estimating equations to examine prevalence and predictors of emotional and physical DRV victimization, perpetration and joint victimization and perpetration. Results More girls reported emotional victimization (28%) and perpetration (18%) than boys (20% and 16%, respectively). More girls (8%) than boys (7%) reported physical perpetration. However, boys (17%) reported more physical victimization than girls (12%). Age-related trajectories of DRV victimization and perpetration were stronger in girls than in boys. Students from single or step parent homes, those in care, and certain ethnic minority groups had increased odds of DRV. No association was found between socioeconomic status and DRV. Conclusions Age-related trajectories and the lack of social patterning by socioeconomic status point to the value of early, universal interventions, while some evidence of ethnic patterning and family structure-related risk factors suggest areas for further research and targeted interventions. DRV continues to be a major public health problem for which little UK-specific intervention evidence exists.

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Oral Antioxidant Vitamins and Magnesium Limit Noise-Induced Hearing Loss by Promoting Sensory Hair Cell Survival: Role of Antioxidant Enzymes and Apoptosis Genes

Antioxidants ◽

10.3390/antiox9121177 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1177

Author(s):

Juan C. Alvarado ◽

Verónica Fuentes-Santamaría ◽

Pedro Melgar-Rojas ◽

María C. Gabaldón-Ull ◽

José J. Cabanes-Sanchis ◽

...

Keyword(s):

Cell Death ◽

Hearing Loss ◽

Antioxidant Enzymes ◽

Oral Administration ◽

Hair Cell ◽

Cell Survival ◽

Sensory Cell ◽

Auditory Function ◽

Sensory Hair ◽

Sensory Hair Cell

Noise induces oxidative stress in the cochlea followed by sensory cell death and hearing loss. The proof of principle that injections of antioxidant vitamins and Mg2+ prevent noise-induced hearing loss (NIHL) has been established. However, effectiveness of oral administration remains controversial and otoprotection mechanisms are unclear. Using auditory evoked potentials, quantitative PCR, and immunocytochemistry, we explored effects of oral administration of vitamins A, C, E, and Mg2+ (ACEMg) on auditory function and sensory cell survival following NIHL in rats. Oral ACEMg reduced auditory thresholds shifts after NIHL. Improved auditory function correlated with increased survival of sensory outer hair cells. In parallel, oral ACEMg modulated the expression timeline of antioxidant enzymes in the cochlea after NIHL. There was increased expression of glutathione peroxidase-1 and catalase at 1 and 10 days, respectively. Also, pro-apoptotic caspase-3 and Bax levels were diminished in ACEMg-treated rats, at 10 and 30 days, respectively, following noise overstimulation, whereas, at day 10 after noise exposure, the levels of anti-apoptotic Bcl-2, were significantly increased. Therefore, oral ACEMg improves auditory function by limiting sensory hair cell death in the auditory receptor following NIHL. Regulation of the expression of antioxidant enzymes and apoptosis-related proteins in cochlear structures is involved in such an otoprotective mechanism.

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Therapeutic Potential of Wnt and Notch Signaling and Epigenetic Regulation in Mammalian Sensory Hair Cell Regeneration

Molecular Therapy ◽

10.1016/j.ymthe.2019.03.017 ◽

2019 ◽

Vol 27 (5) ◽

pp. 904-911 ◽

Cited By ~ 16

Author(s):

Anshula Samarajeewa ◽

Bonnie E. Jacques ◽

Alain Dabdoub

Keyword(s):

Hair Cell ◽

Notch Signaling ◽

Epigenetic Regulation ◽

Therapeutic Potential ◽

Cell Regeneration ◽

Hair Cell Regeneration ◽

Sensory Hair ◽

Sensory Hair Cell

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Insights into sensory hair cell regeneration from the zebrafish lateral line

Current Opinion in Genetics & Development ◽

10.1016/j.gde.2016.05.012 ◽

2016 ◽

Vol 40 ◽

pp. 32-40 ◽

Cited By ~ 39

Author(s):

Jonathan S Kniss ◽

Linjia Jiang ◽

Tatjana Piotrowski

Keyword(s):

Hair Cell ◽

Lateral Line ◽

Cell Regeneration ◽

Hair Cell Regeneration ◽

Sensory Hair ◽

Sensory Hair Cell

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Faculty Opinions recommendation of Therapeutic potential of wnt and notch signaling and epigenetic regulation in mammalian sensory hair cell regeneration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.735560292.793585010 ◽

2021 ◽

Author(s):

Ebenezer Yamoah

Keyword(s):

Hair Cell ◽

Notch Signaling ◽

Epigenetic Regulation ◽

Therapeutic Potential ◽

Cell Regeneration ◽

Hair Cell Regeneration ◽

Sensory Hair ◽

Sensory Hair Cell

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Cytomegalovirus congenital infection – cause of neurosensorial hearing loss

Romanian Journal of Infectious Diseases ◽

10.37897/rjid.2016.2.1 ◽

2016 ◽

Vol 19 (2) ◽

pp. 50-53

Author(s):

Dana-Teodora Anton-Păduraru ◽

◽

Ana Simona Drochioi ◽

Delia Bizim ◽

Angelica-Cristina Marin ◽

...

Keyword(s):

Hearing Loss ◽

Cytomegalovirus Infection ◽

Strong Predictor ◽

Public Health Problem ◽

Congenital Infection ◽

Major Public Health Problem ◽

Seroprevalence Rate ◽

Specific Symptoms ◽

The Relationship

Cytomegalovirus infection is a major public health problem, because annually there are born increasingly more children with this infection. Numerous studies have shown that cytomegalovirus infection is an important cause of hearing loss. Cytomegalovirus infection specific symptoms present at birth are a strong predictor for hearing loss, even in populations with low maternal seroprevalence rate. The severity of deafness due to cytomegalovirus infection is variable. Pathophysiology of deafness caused by cytomegalovirus infection is not well known, the mechanisms possible involved being impaired endolymphatic structures, cytopathic effect of the virus and the host response to the inner ear structures. The relationship between viral load and increased likelihood of deafness in infants supports the role of antiviral therapy in decreasing the incidence and the severity of deafness caused by cytomegalovirus. We consider that monitoring children with congenital cytomegalovirus infection should include also hearing monitoring.

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Isolation of sensory hair cell specific exosomes in human perilymph

10.1101/2021.04.11.439339 ◽

2021 ◽

Author(s):

Pei Zhuang ◽

Suiching Phung ◽

Athanasia Warnecke ◽

Alexandra Arambula ◽

Madeleine St. Peter ◽

...

Keyword(s):

Hearing Loss ◽

Hair Cell ◽

Sensorineural Hearing Loss ◽

Inner Ear ◽

Molecular Characterization ◽

Sensorineural Hearing ◽

Alternative Methods ◽

Sensory Hair ◽

Sensory Hair Cell ◽

Human Inner Ear

AbstractEvaluation of hearing loss patients using clinical audiometry has been unable to give a definitive cellular or molecular diagnosis, hampering the development of treatments of sensorineural hearing loss. However, biopsy of inner ear tissue without losing residual hearing function for pathologic diagnosis is extremely challenging. In a clinical setting, perilymph can be accessed, so alternative methods for molecular characterization of the inner ear may be developed. Recent approaches to improving inner ear diagnostics have been focusing on the evaluation of the proteomic or miRNA profiles of perilymph. Inspired by recent characterization and classification of many neurodegenerative diseases using exosomes which not only are produced in locally in diseased tissue but are transported beyond the blood brain barrier, we demonstrate the isolation of human inner ear specific exosomes using a novel ultrasensitive immunomagnetic nano pom-poms capture-release approach. Using perilymph samples harvested from surgical procedures, we were able to isolate exosomes from sensorineural hearing loss patients in only 2-5 μL of perilymph. By isolating sensory hair cell derived exosomes through their expression level of myosin VII, we for the first time sample material from hair cells in the living human inner ear. This work sets up the first demonstration of immunomagnetic capture-release nano pom-pom isolated exosomes for liquid biopsy diagnosis of sensorineural hearing loss. With the ability to isolate exosomes derived from different cell types for molecular characterization, this method also can be developed for analyzing exosomal biomarkers from more accessible patient tissue fluids such as plasma.

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Sensorineural hearing loss in chronic otitis media: analysis of an overlooked entity!

International Journal of Otorhinolaryngology and Head and Neck Surgery ◽

10.18203/issn.2454-5929.ijohns20193883 ◽

2019 ◽

Vol 5 (5) ◽

pp. 1355

Author(s):

Kishore C. Shetty ◽

Samatha K. Jayaramaiah ◽

Biniyam Kolathingal ◽

Shravan Alva

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Otitis Media ◽

Bone Conduction ◽

Chronic Otitis Media ◽

Public Health Problem ◽

Media Analysis ◽

Sensorineural Hearing ◽

Major Public Health Problem ◽

Cross Sectional

Background: In developing countries, hearing loss continues to be the major public health problem. Among the various causes of hearing loss, chronic otitis media (COM) is one of the commonest. In COM, the presence of sensorineural hearing loss is well established. Our study intends to determine the prevalence of sensorineural hearing loss in chronic otitis media.Methods: This was a cross sectional descriptive study of 151 subjects between the age group of 10 and 60 years. Patients having unilateral chronic otitis media of both mucosal and squamosal types were selected. All patients were evaluated clinically and audiologically. The type, duration of disease and type of perforation is correlated with degree of sensorineural hearing loss. Interaural differences in bone conduction thresholds at 500 Hz, 1 kHz, 2 kHz and 4 kHz were also noted. Results: A statistically significant correlation was noted between type of disease and perforation with hearing loss. A significant interaural difference was noted across the speech frequencies. Sensorineural hearing loss of 19.1% was seen.Conclusions: Significant sensorineural hearing loss is seen in chronic otitis media which was greater in squamosal disease. Statistically significant correlation was noted between type of disease and type of perforation with hearing loss.

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Association of Nutritional Factors with Hearing Loss

Nutrients ◽

10.3390/nu11020307 ◽

2019 ◽

Vol 11 (2) ◽

pp. 307 ◽

Cited By ~ 4

Author(s):

Su Jung ◽

Sang Kim ◽

Seung Yeo

Keyword(s):

Hearing Loss ◽

Protein Intake ◽

Public Health Problem ◽

Major Public Health Problem ◽

Nutritional Factors ◽

Hearing Status ◽

Middle Ear Infection ◽

Lower Protein ◽

Cholesterol Intake ◽

The Relationship

Hearing loss (HL) is a major public health problem. Nutritional factors can affect a variety of diseases, such as HL, in humans. Thus far, several studies have evaluated the association between nutrition and hearing. These studies found that the incidence of HL was increased with the lack of single micro-nutrients such as vitamins A, B, C, D and E, and zinc, magnesium, selenium, iron and iodine. Higher carbohydrate, fat, and cholesterol intake, or lower protein intake, by individuals corresponded to poorer hearing status. However, higher consumption of polyunsaturated fatty acids corresponded to better hearing status of studied subjects. In addition to malnutrition, obesity was reported as a risk factor for HL. In studies of the relationship between middle ear infection and nutrition in children, it was reported that lack of vitamins A, C and E, and zinc and iron, resulted in poorer healing status due to vulnerability to infection. These studies indicate that various nutritional factors can affect hearing. Therefore, considering that multifactorial nutritional causes are responsible, in part, for HL, provision of proper guidelines for maintaining a proper nutritional status is expected to prevent some of the causes and burden of HL.

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