Academic literature on the topic 'Genetic aspects of Deafness, Noise-induced'

Practical relevance: Auditory function is a sense that is central to life for cats - being important in situational awareness of potential predators, pursuit of prey, and for communication with conspecifics, humans and other species. Deafness in cats is most frequently the result of a genetic disorder, strongly associated with white fur and blue eyes, but may also result from acquired causes such as advancing age, ototoxic drugs, infection, environmental noise and physical trauma. Deafness can be sensorineural, where there is loss of cochlear hair cells, or conductive, where sound is muffled on its way to the inner ear. Clinical challenges: Establishing whether a cat is deaf can be difficult as behavioral testing of hearing is subjective and does not reliably detect unilateral deafness. Brainstem auditory evoked response testing is an objective measure but is limited in its availability. Currently, sensorineural deafness is irreversible because no treatments are available to restore lost hair cells. Conductive hearing loss can usually be treated, although full hearing recovery following otitis media may take weeks as the body clears the middle ear of debris. Evidence base: The author draws on the published literature and his extensive research on clinical aspects and molecular genetics of deafness, principally in companion animals, to review types and forms of deafness in cats. He also discusses current diagnostic approaches and provides brief advice for managing cats with hearing loss.

Locust ears have functional and genetic similarities to human ears, including loss of hearing from age or noise exposure. We measured transcript abundances in transcriptomes of noise-exposed and control locust ears. The data indicate remodeling of the ear tympanum and profound reductions in metabolism that may explain reduced sound transduction. These findings advance our understanding of this useful model and suggest further experiments to elucidate mechanisms that ears use to cope with excessive stimulation.

Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1+/− mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.

AbstractProgressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

Abstract Background Age-related hearing loss (ARHL), also known as presbycusis, is the most common sensory impairment seen in elderly people. However, the cochlear aging process does not affect people uniformly, suggesting that both genetic and environmental (e.g., noise, ototoxic drugs) factors and their interaction may influence the onset and severity of ARHL. Considering the potential links between thyroid hormone, mitochondrial activity, and hearing, here, we probed the role of p43, a N-terminally truncated and ligand-binding form of the nuclear receptor TRα1, in hearing function and in the maintenance of hearing during aging in p43−/− mice through complementary approaches, including in vivo electrophysiological recording, ultrastructural assessments, biochemistry, and molecular biology. Results We found that the p43−/− mice exhibit no obvious hearing loss in juvenile stages, but that these mice developed a premature, and more severe, ARHL resulting from the loss of cochlear sensory outer and inner hair cells and degeneration of spiral ganglion neurons. Exacerbated ARHL in p43−/− mice was associated with the early occurrence of a drastic fall of SIRT1 expression, together with an imbalance between pro-apoptotic Bax, p53 expression, and anti-apoptotic Bcl2 expression, as well as an increase in mitochondrial dysfunction, oxidative stress, and inflammatory process. Finally, p43−/− mice were also more vulnerable to noise-induced hearing loss. Conclusions These results demonstrate for the first time a requirement for p43 in the maintenance of hearing during aging and highlight the need to probe the potential link between human THRA gene polymorphisms and/or mutations and accelerated age-related deafness or some adult-onset syndromic deafness.

Hair cells are the mechanosensory receptors of the inner ear and can be damaged by noise, aging, and ototoxic drugs. This damage often results in permanent sensorineural hearing loss. Hair cells have high energy demands and rely on mitochondria to produce ATP as well as contribute to intracellular calcium homeostasis. In addition to generating ATP, mitochondria produce reactive oxygen species, which can lead to oxidative stress, and regulate cell death pathways. Zebrafish lateral-line hair cells are structurally and functionally analogous to cochlear hair cells but are optically and pharmacologically accessible within an intact specimen, making the zebrafish a good model in which to study hair-cell mitochondrial activity. Moreover, the ease of genetic manipulation of zebrafish embryos allows for the study of mutations implicated in human deafness, as well as the generation of transgenic models to visualize mitochondrial calcium transients and mitochondrial activity in live organisms. Studies of the zebrafish lateral line have shown that variations in mitochondrial activity can predict hair-cell susceptibility to damage by aminoglycosides or noise exposure. In addition, antioxidants have been shown to protect against noise trauma and ototoxic drug–induced hair-cell death. In this review, we discuss the tools and findings of recent investigations into zebrafish hair-cell mitochondria and their involvement in cellular processes, both under homeostatic conditions and in response to noise or ototoxic drugs. The zebrafish lateral line is a valuable model in which to study the roles of mitochondria in hair-cell pathologies and to develop therapeutic strategies to prevent sensorineural hearing loss in humans.

Thesis (MAud)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: In developing countries, like Namibia, there is limited data pertaining to the number of individuals with hearing loss and its associated factors. This study aimed to determine the prevalence of potential hearing loss in Namibian Class A mines and to describe the extrinsic and intrinsic factors associated with hearing loss. A cross-sectional design was utilised and data were collected from 132 respondents (mining employees) from five different Class A mines throughout the country. A questionnaire and a retrospective review of respondents’ medical records were utilised to determine the risk factors. The most recent audiogram found in the respondents’ records was used to determine the presence of potential hearing loss. Three definitions of potential hearing loss were used in this study and included all major frequency hearing loss (AFHL), high frequency hearing loss (HFHL) and low frequency hearing loss (LFHL). Potential hearing loss was identified when the pure tone average (PTA) of 0.5, 1, 2, & 4kHz, 0.5, 1 & 2kHz and 4 & 8kHz respectively was greater than 25dBHL in either one or both ears. Chi-square measurements or, where necessary, Fisher’s exact tests, as well as Odds Ratios were used for the analysis of data. In general a significance level of 5% was applied for all analyses. Results indicated the prevalence of potential hearing loss in Namibian mining employees to be 27% and that both extrinsic and intrinsic factors were associated with hearing loss. The extrinsic factors significantly associated with potential hearing loss were both occupational and medical. The occupational factors found to be significant were the number of years employed in whole life >10 years (p=0.012; OR=3.1, 95% CI=1.3-7.9), the number of years employed in current job > 10 years (p=0.01; OR=3.9, 95% CI1.7-8.8) and the non-availability of formal training in prevention of hearing loss (p=0.022; OR=0.3, 95% CI (0.1-0.9). Diabetes was the sole significant extrinsic medical factor (p=0.035, OR=5, 95% CI 1.1-22.1). The only intrinsic factor which was found to be significantly associated with hearing loss was Age, specifically being older than 40 years (p=0.002; OR=3.5, 95% CI 1.6-7.8) and 50 years (p=0.001, OR=5.5, 95% CI1.9-15.8). A multiple logistic regression model of all significant factors found that only no formal training of prevention of hearing loss was found to be significant in the presence of all other factors (p=0.036, OR=0.036, 95% 0.1-0.92). Findings from this study suggest that multiple factors may be associated with potential hearing loss and not just the exposure to hazardous occupational conditions. Recommendations for future research and clinical practice should, therefore, include thorough investigations into the aetiology of hearing loss. As this study focused on Class A mines, it is recommended that future research be conducted in other mines that are not categorised as Class A mines. Keywords: prevalence, extrinsic factors, intrinsic factors, extrinsic occupational factors, extrinsic social factors, extrinsic medical factors, potential hearing loss, mining industry, Class A mine, Namibia.
AFRIKAANSE OPSOMMING: In ontwikkelende lande, soos Namibië, is daar beperkte data met betrekking tot die aantal individue met gehoorverlies en sy verwante faktore. Hierdie studie het gepoog om die voorkoms van gehoorverlies in Namibiese Klas A myne te bepaal en die ekstrinsieke en intrinsieke faktore wat verband hou met potensiale gehoorverlies te beskryf. 'n Deursnee-ontwerp is gebruik en data is ingesamel uit 132 respondente (mynbou werknemers), uit vyf verskillende Klas A myne regdeur die land. 'n Vraelys en 'n retrospektiewe oorsig van die respondente se mediese rekords is gebruik om die risiko faktore te bepaal. Die mees onlangse oudiogram wat in die respondente se rekords gevind is, is gebruik om die teenwoordigheid van potensiale gehoorverlies te bepaal. Drie definisies van potensiale gehoorverlies is gebruik in hierdie studie, ingesluit al die groot frekwensie gehoorverliese (AFHL), hoë frekwensie gehoorverlies (HFHL) en 'n lae frekwensie gehoorverlies (LFHL). ‘n Gehoorverlies was teenwoordig wanneer die suiwer toon gemiddelde (PTA van 0.5 , 1 , 2, & 4kHz , 0.5, 1 & 2kHz en 4 & 8kHz onderskeidelik , groter was as 25dBHL in een of albei ore. Chi -square metings of, waar nodig, Fisher se presiese toetse, asook kans verhoudings is gebruik vir die ontleding van data. In die algemeen is 'n beduidendeidsvlak van 5% gebruik en toegepas vir al die ontledings. Resultate het aangedui die voorkoms van gehoorverlies in Namibiese mynbouwerknemers tot 27 % was en dat beide ekstrinsieke en intrinsieke faktore ‘n verband toon met potensiaal gehoorverlies. Die ekstrinsieke faktore wat ‘n beduidende verband getoon het met gehoorverlies was albei beroeps- en mediese faktore. Die beroepsfaktore wat betekenisvol was, was die aantal jare diens in hele lewe > 10 jaar ( p = 0,012 ; OR = 3.1 , 95 % CI = 1.3-7.9) , die aantal jare in huidige pos> 10 jaar diens (p = 0,01 ; OF = 3.9 , 95 % CI1.7-8.8 ) en die onbeskikbaarheid van formele opleiding in die voorkoming van potensiaal gehoorverlies (p = 0,022 ; OF = 0,3 , 95 % CI ( 0,1-0,9 ). Diabetes was die enigste beduidende ekstrinsieke mediese faktor (p = 0,035 , OR = 5 , 95 % CI 1,1-22,1 ). Die enigste intrinsieke faktor watbeduidend was en verband hou met gehoorverlies was ouderdom, spesifiek om ouer as 40 jaar ( p = 0,002 ; OF = 3.5 , 95 % CI 1,6-7,8 ) en 50 jaar ( p = 0.001 , OR = 5.5 , 95 % CI1.9-15.8 ) te wees. 'n Veelvuldige regressie model van alle beduidende faktore het bevind dat slegs geen formele opleiding in die voorkoming van gerhoor verlies beduidende was in die teenwoordigheid van al die ander faktore ( p = 0,036 , OR = 0,036 , 95 % 0,1-0,92 ) . Bevindinge van hierdie studie dui daarop dat verskeie faktore geassosieer kan word met gehoorverlies en nie net die blootstelling aan gevaarlike beroepstoestande nie. Aanbevelings vir toekomstige navorsing en kliniese praktyk moet dus 'n grondige ondersoek na die etiologie van gehoorverlies uitvoer. Aangesien hierdie studie gefokus het op die Klas A- myne , word dit aanbeveel dat toekomstige navorsing gedoen word in ander myne wat nie gekategoriseer is as Klas A myne nie. Sleutelwoorde: Voorkoms, ekstrinsieke faktore, instrinsieke faktore, ekstrinsieke beroepsfaktore, ekstrinsieke sosiale faktore, ekstrinsieke mediese faktore, potensiale gehoorverlies, Klas A myn, Namibië.

The study investigated the feasibility of including DPOAEs in the annual medical surveillance test battery for the identification of NIHL in a group of employees in a manufacturing industry in KwaZulu-Natal. Feasibility was investigated by exploring the sensitivity, specificity and predictive efficiency of DPOAEs, the ability of DPOAEs to detect subtle noise-induced cochlea changes, the test-retest reliability of DPOAEs and lastly, the duration of time taken to conduct the DPOAE test bilaterally. A cross-sectional and repeated measures within-in participant design was utilized in the study. A purposive convenience sampling technique was used, as well as a stratified sampling approach in order to realize objective two of the study. The study consisted of 60 participants, which were further stratified into four test groups, i.e. Group A: 0-3 years, Group B: 3.1-6 years and Group C: 6.1-9 years and Group D: 9.1-13 years of working within the beverage manufacturing industry. A high sensitivity and negative predictive value was reported in the current study, suggesting that DPOAEs may be able to identify those who present with subtle cochlea changes as a result of exposure to occupational noise. The sensitivity of DPOAEs was 100% at 1, 2, 4, 6 and 8kHz in the right ear and at 4 and 6kHz in the left ear. The specificity of DPOAEs in the current study ranged between 55%-97% across the frequency range in the right ear and 49%-88% in the left ear. A negative predictive value of 100% was obtained bilaterally across the frequency range, except at 8kHz in the left ear. Visual inspection of the DPgram in the current study revealed a bilateral reduction in DPOAE amplitudes for all test groups in the high frequency region of the DP-Gram, namely, 5477Hz and 7303Hz, in the absence of a statistically significant difference (p>0.05). A greater frequency range appears to be affected in this group of workers, indicating that the type of noise, namely, impulse noise, may result in cochlea changes. Corresponding changes on the pure tone audiogram were not observed, however, noise notch configurations were observed for the groups with a longer history of noise exposure. This was not seen bilaterally as is typically expected with NIHL. Good test-retest reliability across the frequency range obtained in the current study further indicates the feasibility of including DPOAEs in the annual medical surveillance test battery. Additionally, the current study calculated an average of 86 seconds (1 minute 26 seconds) to conduct the DPOAE test bilaterally, confirming that DPOAEs are a quick test to administer. The findings of this study suggest that DPOAEs may be used to monitor early subtle noise-induced cochlea changes for workers exposed to noise in the beverage manufacturing industry as part of the annual medical surveillance test battery.
Thesis (M.Comm.Path.)-University of KwaZulu-Natal, Westville, 2013.

AbstractEmerging evidence suggests the growing importance of “nongenetic factors” in the pathogenesis of atherosclerotic vascular disease. Indeed, the inherited genome determines only part of the risk profile as genomic approaches do not take into account additional layers of biological regulation by “epi”-genetic changes. Epigenetic modifications are defined as plastic chemical changes of DNA/histone complexes which critically affect gene activity without altering the DNA sequence. These modifications include DNA methylation, histone posttranslational modifications, and non-coding RNAs and have the ability to modulate gene expression at both transcriptional and posttranscriptional level. Notably, epigenetic signals are mainly induced by environmental factors (i.e., pollution, smoking, noise) and, once acquired, may be transmitted to the offspring. The inheritance of adverse epigenetic changes may lead to premature deregulation of pathways involved in vascular damage and endothelial dysfunction. Here, we describe the emerging role of epigenetic modifications as fine-tuners of gene transcription in atherosclerosis. Specifically, the following aspects are described in detail: (1) discovery and impact of the epigenome in cardiovascular disease, (2) the epigenetic landscape in atherosclerosis; (3) inheritance of epigenetic signals and premature vascular disease; (4) epigenetic control of lipid metabolism, vascular oxidative stress, inflammation, autophagy, and apoptosis; (5) epigenetic biomarkers in patients with atherosclerosis; (6) novel therapeutic strategies to modulate epigenetic marks. Understanding the individual epigenetic profile may pave the way for new approaches to determine cardiovascular risk and to develop personalized therapies to treat atherosclerosis and its complications.