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Pharmacological res...
Pharmacological restoration of visual function in a zebrafish model of von-Hippel Lindau disease
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- Ward, Rebecca (author)
- Univ Coll Dublin, Ireland
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- Ali, Zaheer (author)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten
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- Slater, Kayleigh (author)
- Univ Coll Dublin, Ireland
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- Reynolds, Alison L. (author)
- Univ Coll Dublin, Ireland; Univ Coll Dublin, Ireland
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- Jensen, Lasse (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi
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- Kennedy, Breandan N. (author)
- Univ Coll Dublin, Ireland
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(creator_code:org_t)
- ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020
- 2020
- English.
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In: Developmental Biology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0012-1606 .- 1095-564X. ; 457:2, s. 226-234
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Von Hippel-Lindau (VHL) syndrome is a rare, autosomal dominant disorder, characterised by hypervascularised tumour formation in multiple organ systems. Vision loss associated with retinal capillary hemangioblastomas remains one of the earliest complications of VHL disease. The mortality of Vhl(-/-) mice in utero restricted modelling of VHL disease in this mammalian model. Zebrafish harbouring a recessive germline mutation in the vhl gene represent a viable, alternative vertebrate model to investigate associated ocular loss-of-function phenotypes. Previous studies reported neovascularisation of the brain, eye and trunk together with oedema in the vhl(-/-) zebrafish eye. In this study, we demonstrate vhl(-/-) zebrafish almost entirely lack visual function. Furthermore, hyaloid vasculature networks in the vhl(-/-) eye are improperly formed and this phenotype is concomitant with development of an ectopic intraretinal vasculature. Sunitinib malate, a multi tyrosine kinase inhibitor, market authorised for cancer, reversed the ocular behavioural and morphological phenotypes observed in vhl(-/-) zebrafish. We conclude that the zebrafish yid gene contributes to an endogenous molecular barrier that prevents development of intraretinal vasculature, and that pharmacological intervention with sunitinib can improve visual function and hyaloid vessel patterning while reducing abnormally formed ectopic intraretinal vessels in vhl(-/-) zebrafish.
Subject headings
- NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)
Keyword
- Von Hippel-Lindau; VHL; Retinal neovascularisation; Zebrafish; Sunitinib malate
Publication and Content Type
- ref (subject category)
- art (subject category)
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