PUBLICATION

Hypoxia-induced retinal angiogenesis in zebrafish as a model to study retinopathy

Authors
Cao, R., Jensen, L.D., Söll, I., Hauptmann, G., and Cao, Y.
ID
ZDB-PUB-080728-10
Date
2008
Source
PLoS One   3(7): e2748 (Journal)
Registered Authors
Hauptmann, Giselbert
Keywords
Zebrafish, Medical hypoxia, Vasculogenesis, Angiogenesis, Capillaries, Retinal vessels, Retina, Notch signaling
MeSH Terms
  • Angiogenesis Inhibitors/pharmacology
  • Animals
  • Disease Models, Animal
  • Green Fluorescent Proteins/metabolism
  • Humans
  • Hypoxia*
  • Indoles/pharmacology
  • Microscopy, Confocal
  • Neovascularization, Pathologic*
  • Pyrroles/pharmacology
  • Receptors, Notch/metabolism
  • Retinal Diseases/diagnosis*
  • Retinal Diseases/pathology*
  • Retinal Neovascularization/metabolism
  • Retinal Neovascularization/pathology*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A/metabolism
  • Zebrafish
PubMed
18648503 Full text @ PLoS One
Abstract
Mechanistic understanding and defining novel therapeutic targets of diabetic retinopathy and age-related macular degeneration (AMD) have been hampered by a lack of appropriate adult animal models. Here we describe a simple and highly reproducible adult fli-EGFP transgenic zebrafish model to study retinal angiogenesis. The retinal vasculature in the adult zebrafish is highly organized and hypoxia-induced neovascularization occurs in a predictable area of capillary plexuses. New retinal vessels and vascular sprouts can be accurately measured and quantified. Orally active anti-VEGF agents including sunitinib and ZM323881 effectively block hypoxia-induced retinal neovascularization. Intriguingly, blockage of the Notch signaling pathway by the inhibitor DAPT under hypoxia, results in a high density of arterial sprouting in all optical arteries. The Notch suppression-induced arterial sprouting is dependent on tissue hypoxia. However, in the presence of DAPT substantial endothelial tip cell formation was detected only in optic capillary plexuses under normoxia. These findings suggest that hypoxia shifts the vascular targets of Notch inhibitors. Our findings for the first time show a clinically relevant retinal angiogenesis model in adult zebrafish, which might serve as a platform for studying mechanisms of retinal angiogenesis, for defining novel therapeutic targets, and for screening of novel antiangiogenic drugs.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping