Evaluation of the Hair Cell Regeneration in Zebrafish Larvae by Measuring and Quantifying the Startle Responses

Wang, Changquan; Zhong, Zhenmin; Sun, Peng; Zhong, Hanbing; Li, Hongzhe; Chen, Fangyi

doi:10.1155/2017/8283075

Cited by 19 publications

(14 citation statements)

References 26 publications

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“…Zebrafish larvae show a dose-dependent reduction in rheotaxis (orientation to water flow) after exposure to neomycin or cisplatin ( 135 , 136 ). Other groups have used startle response assays to measure lateral line damage ( 137 , 138 ). While useful, behavioral assays should be interpreted with caution.…”

Section: Models For Ototoxicity Studiesmentioning

confidence: 99%

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings

Coffin

Boney²,

Hill

et al. 2021

Front. Neurol.

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Over 100 drugs and chemicals are associated with permanent hearing loss, tinnitus, and vestibular deficits, collectively known as ototoxicity. The ototoxic potential of drugs is rarely assessed in pre-clinical drug development or during clinical trials, so this debilitating side-effect is often discovered as patients begin to report hearing loss. Furthermore, drug-induced ototoxicity in adults, and particularly in elderly patients, may go unrecognized due to hearing loss from a variety of etiologies because of a lack of baseline assessments immediately prior to novel therapeutic treatment. During the current pandemic, there is an intense effort to identify new drugs or repurpose FDA-approved drugs to treat COVID-19. Several potential COVID-19 therapeutics are known ototoxins, including chloroquine (CQ) and lopinavir-ritonavir, demonstrating the necessity to identify ototoxic potential in existing and novel medicines. Furthermore, several factors are emerging as potentiators of ototoxicity, such as inflammation (a hallmark of COVID-19), genetic polymorphisms, and ototoxic synergy with co-therapeutics, increasing the necessity to evaluate a drug's potential to induce ototoxicity under varying conditions. Here, we review the potential of COVID-19 therapies to induce ototoxicity and factors that may compound their ototoxic effects. We then discuss two models for rapidly detecting the potential for ototoxicity: mammalian auditory cell lines and the larval zebrafish lateral line. These models offer considerable value for pre-clinical drug development, including development of COVID-19 therapies. Finally, we show the validity of in silico screening for ototoxic potential using a computational model that compares structural similarity of compounds of interest with a database of known ototoxins and non-ototoxins. Preclinical screening at in silico, in vitro, and in vivo levels can provide an earlier indication of the potential for ototoxicity and identify the subset of candidate therapeutics for treating COVID-19 that need to be monitored for ototoxicity as for other widely-used clinical therapeutics, like aminoglycosides and cisplatin.

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Section: Models For Ototoxicity Studiesmentioning

confidence: 99%

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings

Coffin

Boney²,

Hill

et al. 2021

Front. Neurol.

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“…The startle response test in zebra sh was carried out following the procedure [40,41] . In this test, 20 zebra sh larvae at 5 dpf were put into the culture dish for free swimming.…”

Section: Startle Response Testmentioning

confidence: 99%

Single-cell RNA-sequencing of zebrafish hair cells reveals the novel genes potentially involved in hearing loss

Qian

Wei

Wang

et al. 2022

Preprint

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Hair cells play key roles in hearing and balance, and hair cell loss would result in hearing loss or vestibular dysfunction. Cellular and molecular research in hair cell biology provide us a better understanding of hearing and deafness. Zebrafish, owing to their hair cell-enriched organs, have been widely applied in hair cell-related research worldwide. Similar to mammals, zebrafish have inner ear hair cells. In addition, they also have lateral line neuromast hair cells. These different hair cells vary in morphology and function. However, systematic analysis of their molecular characteristics remains lacking. In this study, we analyzed the GFP+ cells isolated from Tg(Brn3c:mGFP) larvae using single cell RNA-sequencing (scRNA-seq). Three subtypes of hair cells, namely macula hair cell (MHC), crista hair cell (CHC) and neuromast hair cell (NHC) were characterized and validated by whole-mount in situ hybridization analysis of marker genes. Furthermore, we carried out the morphological comparison of these hair cells. Based on the hair cell scRNA-seq data, we obtained hair cell-enriched genes pool, including hearing loss genes that have been identified in humans and novel genes potentially involved in hair cell formation and function. Two novel genes were discovered to specifically function in NHCs and MHCs, corresponding to their specific expression in NHCs and MHCs. This study allows us to understand the specific genes in hair cell subpopulations of zebrafish, which will shed light on the genetics of both human vestibular and cochlear hair cell function.

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“…Numerous studies have highlighted that the zebrafish is also an excellent model for hearing and balance disorders [71][72][73][74], hair cell death and regeneration, ototoxicity and drug screening [75][76][77][78][79].…”

Section: Zebrafish As a Model Of Deafnessmentioning

confidence: 99%

Use of Zebrafish Models to Boost Research in Rare Genetic Diseases

Crouzier

Richard

Sourbron

et al. 2021

IJMS

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Rare genetic diseases are a group of pathologies with often unmet clinical needs. Even if rare by a single genetic disease (from 1/2000 to 1/more than 1,000,000), the total number of patients concerned account for approximatively 400 million peoples worldwide. Finding treatments remains challenging due to the complexity of these diseases, the small number of patients and the challenge in conducting clinical trials. Therefore, innovative preclinical research strategies are required. The zebrafish has emerged as a powerful animal model for investigating rare diseases. Zebrafish combines conserved vertebrate characteristics with high rate of breeding, limited housing requirements and low costs. More than 84% of human genes responsible for diseases present an orthologue, suggesting that the majority of genetic diseases could be modelized in zebrafish. In this review, we emphasize the unique advantages of zebrafish models over other in vivo models, particularly underlining the high throughput phenotypic capacity for therapeutic screening. We briefly introduce how the generation of zebrafish transgenic lines by gene-modulating technologies can be used to model rare genetic diseases. Then, we describe how zebrafish could be phenotyped using state-of-the-art technologies. Two prototypic examples of rare diseases illustrate how zebrafish models could play a critical role in deciphering the underlying mechanisms of rare genetic diseases and their use to identify innovative therapeutic solutions.

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Evaluation of the Hair Cell Regeneration in Zebrafish Larvae by Measuring and Quantifying the Startle Responses

Cited by 19 publications

References 26 publications

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings

Single-cell RNA-sequencing of zebrafish hair cells reveals the novel genes potentially involved in hearing loss

Use of Zebrafish Models to Boost Research in Rare Genetic Diseases

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