Zebrafish Lacking Circadian Gene per2 Exhibit Visual Function Deficiency

Abstract

The retina has an intrinsic circadian clock, but the importance of this clock for vision is unknown. Zebrafish offer many advantages for studying vertebrate vision and circadian rhythm. Here, we explored the role of zebrafish <i>per2</i>, a light-regulated gene, in visual behavior and the underlying mechanisms. We observed that <i>per2</i> mutant zebrafish larvae showed decreased contrast sensitivity and visual acuity using optokinetic response (OKR) assays. Using a visual motor response (VMR) assay, we observed normal OFF responses but abnormal ON responses in mutant zebrafish larvae. Immunofluorescence showed that mutants had a normal morphology of cone photoreceptor cells and retinal organization. However, electron microscopy showed that <i>per2</i> mutants displayed abnormal and decreased photoreceptor ribbon synapses with arciform density, which resulted in retinal ON pathway defect. We also examined the expression of three cone opsins by quantitative real-time PCR (qRT-PCR), and the expression of long-wave-sensitive opsin (<i>opn1lw</i>) and short-wave-sensitive opsin (<i>opn1sw</i>) was reduced in mutant zebrafish larvae. qRT-PCR analyses also showed a down-regulation of the clock genes <i>cry1ba</i> and <i>bmal1b</i> in the adult eye of <i>per2</i> mutant zebrafish. This study identified a mechanism by which a clock gene affects visual function and defined important roles of <i>per2</i> in retinal information processing.