Abstract
Zebrafish are becoming a popular experimental animal model for vision science and human-inherited retinal diseases. In this chapter, we describe application of zebrafish for the retinitis pigmentosa (RP) caused by digenic LDL receptor-related protein 5 (LRP5) and Eyes shut homolog (EYS). RP is the most common genetic disorder in inherited retinal diseases, and EYS is one of the major causes of RP. EYS orthologs are absent in rodents but present in zebrafish. Using this advantage, we generated and analyzed the digenic eys+/−; low-density lipoprotein (LDL)-related receptor-5 (lrp5)+/− zebrafish, the same form of gene defects emerged from a human case report as a candidate of RP. The analysis discovers that retinol binding protein 1a (rbp1a) gene is remarkably downregulated and that Lrp5 protein is a strong candidate for the receptor of all-trans-retinol in the visual cycle. Furthermore, in this review, we also discuss functional roles of EYS in vertebrates with an emphasis on its possible involvement in the retinal metabolism, the visual cycle, aiming at integrating our findings with recent advances in the research field.