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Hypoxia-induced retinal angiogenesis in zebrafish as a model to study retinopathy
Karolinska Institute, Stockholm, Sweden.
Karolinska Institute, Stockholm, Sweden.
Södertörns University College, Huddinge, Sweden.
Södertörns University College, Huddinge, Sweden.
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2008 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 3, no 7, e2748- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Public Library of Science , 2008. Vol. 3, no 7, e2748- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-92662DOI: 10.1371/journal.pone.0002748PubMedID: 18648503OAI: oai:DiVA.org:liu-92662DiVA: diva2:621515
Available from: 2013-05-15 Created: 2013-05-15 Last updated: 2017-12-06Bibliographically approved

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Jensen, Lasse Dahl

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CiteExportLink to record
Permanent link

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Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf