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 per2, a light-regulated gene, in visual behavior and the underlying mechanisms. We observed that per2 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 per2 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 (opn1lw) and short-wave-sensitive opsin (opn1sw) was reduced in mutant zebrafish larvae. qRT-PCR analyses also showed a down-regulation of the clock genes cry1ba and bmal1b in the adult eye of per2 mutant zebrafish. This study identified a mechanism by which a clock gene affects visual function and defined important roles of per2 in retinal information processing.
Highlights
The circadian clock is an endogenous oscillator that drives daily rhythms in many living systems
We found that the expression of both cacna1fa (P = 0.007 compared with the WT; Figure 3G) and synj1 (P = 0.022 compared with the WT; Figure 3H) was significantly reduced in FIGURE 3 | per2 mutant zebrafish larvae exhibited normal retinal morphology and abnormal photoreceptor ribbon synapses. (A,B) AB-WT and per2−/− zebrafish larval retinas revealed relatively normal retinal morphology by IHC
Clock genes are involved in retinal processing of visual information (Storch et al, 2007; Ait-Hmyed et al, 2013; Mazzotta et al, 2013; Hakkari et al, 2016)
Summary
The circadian clock is an endogenous oscillator that drives daily rhythms in many living systems. The retinal clock was the first extra-SCN circadian oscillator discovered in mammals and is an endogenous circadian clock that regulates many physiological processes within the neural retina (Tosini et al, 2008). In the absence of Rev-erbα, mouse retinas modify the scotopic threshold responses and increase pupillary constriction, thereby increasing the sensitivity to light (Hakkari et al, 2016). These studies defined the important role of the clock component in eye vision research. The molecular mechanisms of circadian rhythm generation in zebrafish appear to have much in common with the more extensively studied mammalian system, the details are different (Cahill, 2002). Data showed that per2−/− zebrafish larvae displayed abnormal photoreceptor ribbon synapses and decreased ribbon synapses with arciform density, which led to visual behavior deficiency compared with the wild-type (WT) fish
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