Pharmacological restoration of visual function in a zebrafish model of von-Hippel Lindau disease

Ward, Rebecca; Ali, Zaheer; Slater, Kayleigh; Reynolds, Alison; Jensen, Lasse; Kennedy, Breandán N.

doi:10.1016/j.ydbio.2019.02.008

Cited by 15 publications

(9 citation statements)

References 29 publications

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“…Larvae treated with emixustat and fenretinide in the dark were morphologically normal, other than they did not inflate their swim bladder ( Figure 2D) as also observed under a normal light/dark cycle ( Figure 1C). An uninflated swim bladder is commonly observed in visually compromised zebrafish larvae (40,41). Interestingly, neither 50 μM emixustat nor 10 μM fenretinide induced obvious changes in retinal histology, particularly the photoreceptor outer segment structure and RPE, compared to vehicle controls ( Figure 2E-G, 2E'-2G').…”

Section: In Dark Adapted Zebrafish Emixustat Blocks Immediate Photopmentioning

confidence: 94%

Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision

Ward

Kaylor

Cobice³

et al. 2020

Preprint

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Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters (atRE) to 11-cis-retinol (11cROL) is mediated by the retinoid isomerohydrolase Rpe65. An alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early and late phases of cone photopic vision. In zebrafish larvae raised under

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Section: In Dark Adapted Zebrafish Emixustat Blocks Immediate Photopmentioning

confidence: 94%

Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision

Ward

Kaylor

Cobice³

et al. 2020

Preprint

Self Cite

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“…In this frame, vhl mutants have been recently used to test the efficacy of several compounds in rescuing VHL phenotype. For instance, it has been demonstrated that sunitinib malate, a multi-tyrosine kinase inhibitor, was able to reverse the ocular, behavioral and morphological phenotypes observed in homozygous vhl zebrafish mutants (Ward et al 2019). Therefore, these mutants represent a promising platform not only to study molecular basis of VHL disease, but also to identify innovative treatments for this complex pathology.…”

Section: Genetic Modelsmentioning

confidence: 99%

Fishing for neuroendocrine tumors

Gaudenzi

Carra

Dicitore

et al. 2020

Endocrine-Related Cancer

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Neuroendocrine tumors (NETs) are a class of rare and heterogeneous neoplasms that originate from the neuroendocrine system. In several cases, these neoplasms can release bioactive hormones leading to characteristic clinical syndromes and hormonal dysregulations with detrimental impact on the quality of life and survival of these patients. Only few animal models are currently available to investigate pathogenesis, progression and functional syndromes in NETs and to identify new therapeutic strategies. The tropical teleost zebrafish (Danio rerio) is a popular vertebrate model system that offers unique advantages for the study of several biological processes, ranging from embryonic development to human diseases such as cancer. In this review, we summarize recent advances on zebrafish models for NET preclinical research that take advantage of modern genetic and transplantable technologies. In the future, these tools may have a role in the treatment decision-making and tertiary prevention of NETs.

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“…Zebrafish larvae and embryos have long been used to assay environmental toxicants. 2,3,8,30 They have also made waves in neuroscience as models for vision, 7,9,21,37,49 threat response, 38 memory, 52 algesia, 6,14,44 and sleep. 35,39,43 In a rare example of bench-to-bedside, the FDA approved the drug lorcaserin as an antiepileptic, based mostly on evidence in zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous analysis of neuroactive compounds in zebrafish

Myers-Turnbull

Taylor

Helsell

et al. 2020

Preprint

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Purpose: Compounds that act on the central nervous system (CNS) are crucial tools in drug discovery and neuroscience. To discover compounds with novel mechanisms of action, researchers have developed behavioral screens in larval zebrafish including various methods to identify and classify hit compounds. However, these methods typically do not admit intuitive numerical scores of screen performance. This study describes methods to classify compounds simultaneously in zebrafish and quantify screen performance.Methods: We collected randomized, highly replicated data for two sets of compounds: 16 quality-control (QC) compounds and a reference set of 648 known CNS ligands. Machine learning models were trained to discriminate between compound-induced phenotypes, compare performance between protocols, and detect hit compounds.Results: Classification accuracy on the QC set was 94.3%. In addition, 106 of 648 CNS ligands were identified as phenotypically active, and hits were enriched for dopaminergic and serotonergic targets. The raw data is included to facilitate replication and data mining.Significance: This study describes methods to evaluate behavioral phenotyping assays, which can be used to facilitate comparison and standardization of data within the zebrafish phenotyping community.

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Pharmacological restoration of visual function in a zebrafish model of von-Hippel Lindau disease

Cited by 15 publications

References 29 publications

Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision

Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision

Fishing for neuroendocrine tumors

Simultaneous analysis of neuroactive compounds in zebrafish

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