DOI: 10.1101/485730Dec 4, 2018Paper

Pharmacological Restoration of Visual Function in a Zebrafish Model of von-Hippel Lindau Disease

BioRxiv : the Preprint Server for Biology
Rebecca WardBreandán N Kennedy


Von Hippel-Lindau (VHL) syndrome is rare, autosomal dominant disorder, characterized 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, alterative vertebrate model to investigate associated ocular loss-of-function phenotypes. Previous studies reported neovascularization 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, 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 vhl gene contributes to an endogenous molecular barrier that prevents development of intraretinal vasculature, and that ...Continue Reading

Related Concepts

Blood Vessel
Malignant Neoplasms
Von Hippel-Lindau Syndrome
Laboratory mice

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