Application of zebrafish oculomotor behavior to model human disorders

Maurer, Colette M.; Huang, Yingyu

doi:10.1515/rns.2011.003

Cited by 36 publications

(35 citation statements)

References 87 publications

(101 reference statements)

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“…[17][18][19][20][21][22][23][24][25][26][27] The lens in zebrafish eyes is spheroid and not ellipsoid as compared with the human eye, and as a consequence, the zebrafish eye has a much lower volume of vitreous compared with the human eye ( Figure 1a). …”

Section: Eye Structurementioning

confidence: 99%

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

129

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: Eye Structurementioning

confidence: 99%

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

129

114

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“…Their precocious development of vision and remarkable evolutionary conservation of the eye make the zebrafish retina an excellent model for human visual disorders. [13][14][15][16] Another advantage of the zebrafish as a model for human retinal disease is their cone-dominant retina, opening the possibility to specifically analyze cone-mediated disorders that are more difficult to study in the rod dominant nocturnal mouse. Robust visually-guided assays, including the optomotor and optokinetic tests allow quantitative measurements of visual impairment in zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Gucy2f zebrafish knockdown – a model for Gucy2d-related leber congenital amaurosis

et al. 2012

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Mutations in retinal-specific guanylate cyclase (Gucy2d) are associated with Leber congenital amaurosis-1 (LCA1). Zebrafish offer unique advantages relative to rodents, including their excellent color vision, precocious retinal development, robust visual testing strategies, low cost, relatively easy transgenesis and shortened experimental times. In this study we will demonstrate the feasibility of using gene-targeting in the zebrafish as a model for the photoreceptor-specific GUCY2D-related LCA1, by reporting the visual phenotype and retinal histology resulting from Gucy2f knockdown. Gucy2f zebrafish LCA-orthologous cDNA was identified and isolated by PCR amplification. Its expression pattern was determined by whole-mount in-situ hybridization and its function was studied by gene knockdown using two different morpholino-modified oligos (MO), one that blocks translation of Gucy2f and one that blocks splicing of Gucy2f. Visual function was assessed with an optomotor assay on 6-days-postfertilization larvae, and by analyzing changes in retinal histology. Gucy2f knockdown resulted in significantly lower vision as measured by the optomotor response compared with uninjected and control MO-injected zebrafish larvae. Histological changes in the Gucy2f-knockdown larvae included loss and shortening of cone and rod outer segments. A zebrafish model of Gucy2f-related LCA1 displays early visual dysfunction and photoreceptor layer dystrophy. This study serves as proof of concept for the use of zebrafish as a simple, inexpensive model with excellent vision on which further study of LCA-related genes is possible. Keywords: leber congenital amaurosis; animal model; GUCY2D; optomotor assay INTRODUCTION Leber congenital amaurosis (LCA) is a family of severe, early-onset, autosomal-recessive forms of pediatric blindness. LCA has been linked to more than 16 genes, often exhibiting clinical heterogeneity. 1,2 LCA1 is caused by mutations in the gene GUCY2D, which encodes the retinal Gucy2d-1 (GC1) and accounts for B20% of all cases of LCA. 3 LCA2 is caused by mutations in the RPE65 gene, which is expressed in the retinal pigment epithelium. Breakthrough research has demonstrated visual improvement following gene therapy trials in humans with LCA2. 4,5 Human trials relied on a decade of proof-of-concept studies in canine and rodent models. 6-8 Unlike LCA2, in which gene therapy is aimed at correcting an RPE defect, searching for gene therapy for LCA1 will involve an attempt at treating the photoreceptors. European Journal of Human GeneticsResearch in inherited retinal disease relies heavily on animal models, commonly mammals such as mice and dogs. These animal models have significant advantages, including the availability of knockout technology. Two specific drawbacks slow the applicability of rodent or canine models for study of relatively rare genetic diseases such as LCA and other retinal dystrophies. The first difficulty is the high cost and length of time required to create a new knockout line; thus, it is applicable only for comm...

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“…The OKR is triggered by a velocity and direction input coming from the retina and encoded by a neural circuit involving pretectal nuclei ( 1,2 ) .…”

Section: Introductionmentioning

confidence: 99%

“…Zebra fi sh are lateral eyed, and binocular overlap is minimal since all axons from the optic nerve cross at the optic chiasm and project to the contralateral brain side. Humans have frontally positioned eyes and binocular vision, since around half of the axons project to the ipsilateral brain side ( 2 ) . These differences allow us to study the OKR in zebra fi sh without the complications of smooth pursuit and binocular vision.…”

Section: Introductionmentioning

confidence: 99%

“…We then describe our standard eye movement quanti fi cation approach which allows for detection of subjects with vision defects as well as for investigation of the OKR behavior itself. Since our system is under continuous development ( 1,2,11,13,16,17 ) , some of the details described in the protocol may change over time. However, our detailed protocol should enable the reader to apply the methodology of quantitative OKR measurements.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Optokinetic Response in Zebrafish by Computer-Based Eye Tracking

Huber‐Reggi

Mueller

2012

Methods in Molecular Biology

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Large-fi eld movements in the visual surround trigger spontaneous, compensatory eye movements known as optokinetic response (OKR) in all vertebrates. In zebra fi sh ( Danio rerio ) the OKR is well developed at 5 days post fertilization and can be used in the laboratory for screening of visual performance following genetic manipulations or pharmaceutical treatments. Several setups for measurement of the zebra fi sh OKR have been described. All of them are based on the presentation of moving gratings to the larva or to the adult fi sh. However, they differ in the way of presenting gratings and in the method of analysis. Here, we describe a detailed protocol for our newest software that enables computer-generation of the moving stripes and automatic tracking of eye movement. This protocol makes it possible to quantitatively measure OKR in both larvae and adult fi shes in a fast and reliable way.

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Application of zebrafish oculomotor behavior to model human disorders

Cited by 36 publications

References 87 publications

Zebrafish—on the move towards ophthalmological research

Zebrafish—on the move towards ophthalmological research

Gucy2f zebrafish knockdown – a model for Gucy2d-related leber congenital amaurosis

Analysis of Optokinetic Response in Zebrafish by Computer-Based Eye Tracking

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