Cholecystokinin receptor type A are involved in the circadian rhythm of the mouse retina

• Published in: Heliyon 2024-06, Vol.10 (12), p.e32653, Article e32653
• Main Authors: Yamakawa, Yusuke, Tsurudome, Yuya, Tamada, Masaki, Tsuchimochi, Yuki, Umeda, Yuya, Yoshida, Yuya, Kobayashi, Daisuke, Kawashiri, Takehiro, Kubota, Toshio, Matsunaga, Naoya, Shimazoe, Takao
• Format: Article
• Language: English
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e32653

The retina is the only organ projecting external light to the suprachiasmatic nucleus. Cholecystokinin receptor type A (Cckar/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 Cckar mRNA expression in retinal cells exhibited diurnal variations. The rhythm of expression of the clock gene Per1/Per2 in retinal cells was altered in Cckar−/− 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 Per2 transcription, which was altered in a time-dependent manner relative to the Per2 expression. Light irradiation studies in Cckar−/− mice did not exhibit an increase in Period expression in the suprachiasmatic nucleus. These results indicate that Cckar is among the factors that regulate the cycle of clock genes on the retina. Cckar knockout attenuates the light responsiveness of suprachiasmatic nucleus and reduces the expression amplitude of Period genes in the retina. Thus, Cckar may contribute to entrainment of the light environment and maintenance of the expression cycle of Period gene, which is one of the core clock genes. Schematic diagram showing that Cckar-CCK signaling is involved in the light responsiveness of clock genes in retinal cells and SCN. [Display omitted] •Cckar mRNA expression in retinal cells exhibits daily fluctuations.•Absence of Cckar alters the rhythm of Per1/Per2 mRNA expression in retinal cells.•Cckar plays a pivotal role in light perception in retinal cells.•Lorglumide, an inhibitor of Cckar, attenuates photoresponsiveness in retinal cells.•Cckar regulates Period gene amplitude strength in retinal cells.