Genetics of photoreceptor degeneration and regeneration in zebrafish

Brockerhoff, Susan E.; Fadool, James M.

doi:10.1007/s00018-010-0563-8

Cited by 64 publications

(60 citation statements)

References 75 publications

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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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Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…However, because the development of the retina and its morphology are remarkably conserved in all vertebrates, non-mammalian species have also emerged during the last decade as alternative valuable models. In particular, zebrafish, which is well suited for large-scale genetic screens, revealed to be very informative in the elucidation of the processes underlying retina degeneration (reviewed in Bibliowicz et al, 2011;Brockerhoff and Fadool, 2011;. Its importance is strengthened by the fact that not all the murine models are suitable to mimic a particular pathological feature or for the development of pharmacological therapies.…”

Section: Alternative Models For Retina Degenerationmentioning

confidence: 99%

Advances in Regenerative Medicine

Schantz¹,

Hutmacher²

2016

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“…For example, in liver regeneration, larger damage of the adult liver lobes usually makes fish die quickly. Other physical injuries are also applied, for example, laser targeted cell ablation is mainly used to induce lesions of retina photoreceptor and heart muscles recently [8,15]. Chemical injury is based on the toxicity of the compounds to the target organs.…”

Section: Organ Injury Approaches Applied In Zebrafishmentioning

confidence: 99%

“…However, continual neurogenesis and regenerative capability have been demonstrated in zebrafish [13]. The studies of zebrafish CNS regeneration are mainly divided into three fields: adult neurons in the brain in particular in the telencephalon after physical lesion, spinal cord or axon restoration after truncation, and retina (photoreceptor) regeneration [3, 8,9,13]. It is currently in general believed that the regenerative features of zebrafish CNS depend on the continually proliferative stem/progenitor cells and the permissive environments [13,55,56].…”

Section: Cns Regenerationmentioning

confidence: 99%

Using zebrafish as the model organism to understand organ regeneration

Shi

Fang

et al. 2015

Sci. China Life Sci.

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The limited regenerative capacity of several organs, such as central nervous system (CNS), heart and limb in mammals makes related major diseases quite difficult to recover. Therefore, dissection of the cellular and molecular mechanisms underlying organ regeneration is of great scientific and clinical interests. Tremendous progression has already been made after extensive investigations using several model organisms for decades. Unfortunately, distance to the final achievement of the goal still remains. Recently, zebrafish became a popular model organism for the deep understanding of regeneration based on its powerful regenerative capacity, in particular the organs that are limitedly regenerated in mammals. Additionally, zebrafish are endowed with other advantages good for the study of organ regeneration. This review summarizes the recent progress in the study of zebrafish organ regeneration, in particular regeneration of fin, heart, CNS, and liver as the representatives. We also discuss reasons of the reduced regenerative capacity in higher vertebrate, the roles of inflammation during regeneration, and the difference between organogenesis and regeneration. organ regeneration, zebrafish, fin, heart, liver, CNS Citation:Shi WC, Fang ZB, Li L, Luo LF. Using zebrafish as the model organism to understand organ regeneration.

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Genetics of photoreceptor degeneration and regeneration in zebrafish

Cited by 64 publications

References 75 publications

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

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

Advances in Regenerative Medicine

Using zebrafish as the model organism to understand organ regeneration

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