Genetic determinants of hyaloid and retinal vasculature in zebrafish

Álvarez, Yolanda; Cederlund, Maria L.; Cottell, David C.; Bill, Brent R.; Ekker, Stephen C.; Torres-Vázquez, Jesús; Weinstein, Brant M.; Hyde, David R.; Vihtelic, Thomas S.; Kennedy, Breandán N.

doi:10.1186/1471-213x-7-114

Cited by 142 publications

(179 citation statements)

References 62 publications

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“…There is a growing interest in the use of zebrafish in DR due to the fact that they exhibit similar retinal vascular physiology and pathology compared with mammals. 95 Hyperglycaemic zebrafish are shown to have similar retinal structure abnormalities as seen in diabetic patients. 96 Hyperglycaemia can be induced in adult zebrafish by immersing alternately in glucose solution and water over 28 days followed by retinal examination.…”

Section: Drmentioning

confidence: 91%

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

135

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: Drmentioning

confidence: 91%

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

135

114

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“…89 Importantly, zebrafish obd mutants survive to adulthood unlike knock-out mice, enabling characterisation of the hyaloid vasculature.…”

Section: Vascular Diseasementioning

confidence: 99%

The zebrafish eye—a paradigm for investigating human ocular genetics

Richardson¹,

Tracey‐White²,

Webster

et al. 2016

Eye

147

162

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Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future.

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“…15 However, there are some contradictory reports that VEGF expression is enhanced rather than decreased in the lens during HVS regression and remains in the adult. 16,17 Thus, although VEGF is crucial for VECs stability, apoptosis of VEC may be independent on VEGF during HVS regression. Altogether, it has been accepted that cell-cell interaction between macrophages, endothelial cells, and pericytes is crucial for the HVS regression.…”

mentioning

confidence: 99%

Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development

et al. 2009

Cell Death Differ

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Developmental tissues go through regression, remodeling, and apoptosis. In these processes, macrophages phagocytize dead cells and induce apoptosis directly. In hyaloid vascular system (HVS), macrophages induce apoptosis of vascular endothelial cells (VECs) by cooperation between the Wnt and angiopoietin (Ang) pathways through cell-cell interaction. However, it remains unclear how macrophages are activated and interact with VECs. Here we show that Ninjurin1 (nerve injury-induced protein; Ninj1) was temporally increased in macrophages during regression of HVS and these Ninj1-expressing macrophages closely interacted with hyaloid VECs. Systemic neutralization using an anti-Ninj1 antibody resulted in the delay of HVS regression in vivo. We also found that Ninj1 increased cell-cell and cell-matrix adhesion of macrophages. Furthermore, Ninj1 stimulated the expression of Wnt7b in macrophages and the conditioned media from Ninj1-overexpressing macrophages (Ninj1-CM) decreased Ang1 and increased Ang2 in pericytes, which consequently switched hyaloid VEC fate from survival to death. Collectively, these findings suggest that macrophages express Ninj1 to increase the death signal through cell-cell interaction and raise the possibility that Ninj1 may act similarly in other developmental regression mediated by macrophages.

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Genetic determinants of hyaloid and retinal vasculature in zebrafish

Cited by 142 publications

References 62 publications

Zebrafish—on the move towards ophthalmological research

Zebrafish—on the move towards ophthalmological research

The zebrafish eye—a paradigm for investigating human ocular genetics

Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development

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