Advances In Zebrafish Chemical Screening Technologies

Mathias, Jonathan R.; Saxena, Mohit; Mumm, Jeff S.

doi:10.4155/fmc.12.115

Cited by 75 publications

(61 citation statements)

References 87 publications

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“…In addition, embryos are permeable to many small molecules allowing easy administration of drugs. 8 Embryonic development in zebrafish is rapid and takes only few days with the majority of organs such as brain, heart, liver, intestine, and eye developing within 24 h and becoming functional within a week. The free-swimming larvae hatch from around 72 h post fertilization (hpf) and soon start foraging for food.…”

Section: Zebrafish As An Animal Modelmentioning

confidence: 99%

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

136

114

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Millions of people are affected by visual impairment and blindness globally, and the prevalence of vision loss is likely to increase as we are living longer. However, many ocular diseases remain poorly controlled due to lack of proper understanding of the pathogenesis and the corresponding lack of effective therapies. Consequently, there is a major need for animal models that closely mirror the human eye pathology and at the same time allow higher-throughput drug screening approaches. In this context, zebrafish as an animal model organism not only address these needs but can in many respects reflect the human situation better than the current rodent models. Over the past decade, zebrafish have become an established model to study a variety of human diseases and are more recently becoming a valuable tool for the study of human ophthalmological disorders. Many human ocular diseases such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration have already been modelled in zebrafish. In addition, zebrafish have become an attractive model for pre-clinical drug toxicity testing and are now increasingly used by scientists worldwide for the discovery of novel treatment approaches. This review presents the advantages and uses of zebrafish for ophthalmological research.

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Section: Zebrafish As An Animal Modelmentioning

confidence: 99%

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

136

114

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“…12 Furthermore, potential organ-specific drug toxicity problems can be rapidly identified using zebrafish transgenic models. [13][14] Compound library screens can also be performed with a remarkable throughput in contrats to conventional rodent models [15][16][17] Notwithstanding this, laboratory automation of in-situ analysis using zebrafish embryo and larvae is still deeply in its infancy. The major hurdle to widespread deployment of zebrafish embryo and larvae in large-scale drug development projects is lack of enabling high-throughput analytical platforms.…”

Section: Introductionmentioning

confidence: 99%

An integrated micromechanical large particle in flow sorter (MILPIS)

et al. 2015

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At present, the major hurdle to widespread deployment of zebrafish embryo and larvae in large-scale drug development projects is lack of enabling high-throughput analytical platforms. In order to spearhead drug discovery with the use of zebrafish as a model, platforms need to integrate automated pre-test sorting of organisms (to ensure quality control and standardization) and their in-test positioning (suitable for high-content imaging) with modules for flexible drug delivery. The major obstacle hampering sorting of millimetre sized particles such as zebrafish embryos on chip-based devices is their substantial diameter (above one millimetre), mass (above one milligram), which both lead to rapid gravitational-induced sedimentation and high inertial forces. Manual procedures associated with sorting hundreds of embryos are very monotonous and as such prone to significant analytical errors due to operator's fatigue. In this work, we present an innovative design of a micromechanical large particle in-flow sorter (MILPIS) capable of analysing, sorting and dispensing living zebrafish embryos for drug discovery applications. The system consisted of a microfluidic network, revolving micromechanical receptacle actuated by robotic servomotor and opto-electronic sensing module. The prototypes were fabricated in poly(methyl methacrylate) (PMMA) transparent thermoplastic using infrared laser micromachining. Elements of MILPIS were also fabricated in an optically transparent VisiJet resin using 3D stereolithography (SLA) processes (ProJet 7000HD, 3D Systems). The device operation was based on a rapidly revolving miniaturized mechanical receptacle. The latter function was to hold and position individual fish embryos for (i) interrogation, (ii) sorting decision-making and (iii) physical sorting..The system was designed to separate between fertilized (LIVE) and non-fertilized (DEAD) eggs, based on optical transparency using infrared (IR) emitters and receivers embedded in the system. Digital oscilloscope were used to distinguish the diffraction signals from IR sensors when both LIVE and DEAD embryos were flow through in the chip. Image process analysis were also used as detection module to track DEAD embryos as it flowed in the channel. ; phone 61 3 992 57157; fax 61 3 992 57110; http://www.rmit.edu.au/staff/donald-wlodkowic

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“…Further, there have been numerous scientific and technological advances to make chemical genetic screens possible and manageable [16][17][18][19][20] . Peterson and colleagues were the first to use zebrafish in a chemical genetic screen in 2000, and later in 2004 identified a compound that suppressed an aortic coarctation mutation in zebrafish 21,22 .…”

Section: Introductionmentioning

confidence: 99%

“…These chemical genetic screens broadly demonstrate the utility of testing small compounds in the developing zebrafish and the ability to apply chemical genetics to interrogate adult tissue function. Furthermore, there is a growing list of commercially available pharmacology collections that are available for academic studies 19 .…”

Section: Introductionmentioning

confidence: 99%

A Manual Small Molecule Screen Approaching High-throughput Using Zebrafish Embryos

Poureetezadi

Donahue

Wingert

2014

JoVE

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Zebrafish have become a widely used model organism to investigate the mechanisms that underlie developmental biology and to study human disease pathology due to their considerable degree of genetic conservation with humans. Chemical genetics entails testing the effect that small molecules have on a biological process and is becoming a popular translational research method to identify therapeutic compounds. Zebrafish are specifically appealing to use for chemical genetics because of their ability to produce large clutches of transparent embryos, which are externally fertilized. Furthermore, zebrafish embryos can be easily drug treated by the simple addition of a compound to the embryo media. Using whole-mount in situ hybridization (WISH), mRNA expression can be clearly visualized within zebrafish embryos. Together, using chemical genetics and WISH, the zebrafish becomes a potent whole organism context in which to determine the cellular and physiological effects of small molecules. Innovative advances have been made in technologies that utilize machine-based screening procedures, however for many labs such options are not accessible or remain cost-prohibitive. The protocol described here explains how to execute a manual high-throughput chemical genetic screen that requires basic resources and can be accomplished by a single individual or small team in an efficient period of time. Thus, this protocol provides a feasible strategy that can be implemented by research groups to perform chemical genetics in zebrafish, which can be useful for gaining fundamental insights into developmental processes, disease mechanisms, and to identify novel compounds and signaling pathways that have medically relevant applications.

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Advances In Zebrafish Chemical Screening Technologies

Cited by 75 publications

References 87 publications

Zebrafish—on the move towards ophthalmological research

Zebrafish—on the move towards ophthalmological research

An integrated micromechanical large particle in flow sorter (MILPIS)

A Manual Small Molecule Screen Approaching High-throughput Using Zebrafish Embryos

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