UTILIZING ZEBRAFISH TO MODEL THE CHILDHOOD BLINDING DISORDER, FAMILIAL EXUDATIVE VITREORETINOPATHY (FEVR), AND DISCOVER NOVEL THERAPEUTICS

Abstract

Familial exudative vitreoretinopathy (FEVR) is a blinding disorder that results in incomplete peripheral retinal vascularization at birth and there is currently no treatment. Zebrafish were used as a model to mimic a FEVR-like phenotype in order to carry out a preliminary drug screen for novel therapeutic compounds. A novel FEVR gene, cdh5, was knocked down using morpholino oligonucleotide and displayed a robust retinal phenotype and smaller eye size. Sphinghosine-1 phosphate receptor-2 (S1PR2) is a known inhibitor of blood vessel development. Several compounds predicted to interact with S1PR2 were screened using the cdh5 morphant zebrafish including an S1PR2 inhibitor; JTE-013. JTE-013 significantly improved eye size establishing that S1PR2 can be targeted in zebrafish. “Compound 1” significantly decreased eye size, whereas “compound 2” had no effect. Thus, S1PR2 is a possible pharmacological target for the treatment of FEVR.