Yamakawa Yusuke, Tsurudome Yuya, Tamada Masaki, Tsuchimochi Yuki, Umeda Yuya, Yoshida Yuya, Kobayashi Daisuke, Kawashiri Takehiro, Kubota Toshio, Matsunaga Naoya, Shimazoe Takao
Department of Clinical Pharmacy and Pharmaceutical Care, Kyushu University, Fukuoka, Japan.
Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan.
Heliyon. 2024 Jun 7;10(12):e32653. doi: 10.1016/j.heliyon.2024.e32653. eCollection 2024 Jun 30.
The retina is the only organ projecting external light to the suprachiasmatic nucleus. Cholecystokinin receptor type A (Cckar/) is one of the essential factors for light reception in retinal cells. As there was a lack of literature on the matter, we aimed to elucidate the cause of the time-dependent phase change in clock gene expression. We found that mRNA expression in retinal cells exhibited diurnal variations. The rhythm of expression of the clock gene / in retinal cells was altered in mice. The light sensitivity of retinal cells was evaluated in wild-type mice, which showed c-Fos was activated in the ganglion cell layer more than in the inner granular layer. This increase in the number of c-Fos-positive cells was suppressed by lorglumide, a Cckar antagonist. Treatment of rat retina primary cells with lorglumide suppressed transcription, which was altered in a time-dependent manner relative to the expression. Light irradiation studies in mice did not exhibit an increase in expression in the suprachiasmatic nucleus. These results indicate that Cckar is among the factors that regulate the cycle of clock genes on the retina. knockout attenuates the light responsiveness of suprachiasmatic nucleus and reduces the expression amplitude of genes in the retina. Thus, Cckar may contribute to entrainment of the light environment and maintenance of the expression cycle of gene, which is one of the core clock genes.
视网膜是唯一将外部光线投射到视交叉上核的器官。A 型胆囊收缩素受体（Cckar/）是视网膜细胞光接收的关键因素之一。由于缺乏关于此问题的文献，我们旨在阐明时钟基因表达中时间依赖性相位变化的原因。我们发现视网膜细胞中的 mRNA 表达呈现昼夜变化。在 小鼠中，视网膜细胞中时钟基因/的表达节律发生了改变。在野生型小鼠中评估了视网膜细胞的光敏感性，结果显示神经节细胞层中的 c-Fos 激活程度高于内颗粒层。Cckar 拮抗剂洛谷胺抑制了 c-Fos 阳性细胞数量的增加。用洛谷胺处理大鼠视网膜原代细胞抑制了 转录，其相对于 表达呈时间依赖性改变。对 小鼠的光照研究未显示视交叉上核中 表达增加。这些结果表明，Cckar 是调节视网膜上时钟基因周期的因素之一。 基因敲除减弱了视交叉上核的光反应性，并降低了视网膜中 基因的表达幅度。因此，Cckar 可能有助于光环境的同步以及核心时钟基因之一的 基因表达周期的维持。
