Does pharmacological intervention attenuate hallmarks of ocular cancer or blindness in a zebrafish model of Von Hippel-Lindau Disease? (360G-Wellcome-207176_Z_17_Z)

Von Hippel-Lindau (VHL) disease is an autosomal dominant condition affecting 1 in 36000 people. VHL is characterised by the formation of multiple benign and malignant neoplasms. Retinal hemiangioblastomas (RH) are the most common manifestation of VHL disease, presenting in up to 85% of patients. Vision loss is a common clinical presentation in VHL patients as current therapies are invasive and not effective. Furthermore, removal of RH is restricted to the peripheral retina. Although zebrafish do not develop RH, they are a useful in vivo model in the vhl studies as they possess many hallmarks associated with the disease. Defects in the vhl tumour suppressor gene leads to a systemic hypoxic response and subsequent uncontrolled blood vessel development in vivo. Ectopic and vasculature leakage has previously been shown in the vhl zebrafish model. This research aims to investigate the efficacy of a commonly used anti-angiogenic compounds (quininib analogues), in reducing the angiogenic hallmarks displayed by vhl patients. Its ability to rescue or improve visual function will be measured and endpoints will employ behavioural and morphological analysis.