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Melatonin signaling affects the timing in the daily rhythm of phagocytic activity by the retinal pigment epithelium

机译:褪黑素信号传导通过视网膜色素上皮影响吞噬活动的每日节律的时间安排

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摘要

Earlier studies in Xenopus have indicated a role for melatonin in the regulation of retinal disk shedding, but the role of melatonin in the regulation of daily rhythm in mammalian disk shedding and phagocytosis is still unclear. We recently produced a series of transgenic mice lacking melatonin receptor type1 (MT1) or type 2 (MT2) in a melatonin-proficient background and have shown that removal of MT1 and MT2 receptors induces significant effects on daily and circadian regulation of the electroretinogram as well as on the viability of photoreceptor cells during aging. In this study we investigated the daily rhythm of phagocytic activity by the retinal pigment epithelium in MT1 and MT2 knock-out mice. Our data indicate that in MT1 and MT2 knock-out mice the peak of phagocytosis is advanced by 3 h with respect to wild-type mice and occurred in dark rather than after the onset of light, albeit the mean phagocytic activity over the 24-h period did not change among the three genotypes. Nevertheless, this small change in the profile of daily phagocytic rhythms may produce a significant effect on retinal health since MT1 and MT2 knock-out mice showed a significant increase in lipofuscin accumulation in the retinal pigment epithelium.
机译:在非洲爪蟾的早期研究表明褪黑激素在调节视网膜盘脱落中的作用,但褪黑素在哺乳动物盘脱落和吞噬作用中日常节律的调节作用尚不清楚。我们最近生产了一系列在褪黑激素熟练的背景中缺乏褪黑激素受体1型(MT1)或2型(MT2)的转基因小鼠,并表明去除MT1和MT2受体也对视网膜电图的日常和昼夜节律调节产生重大影响如感光细胞在衰老过程中的生存能力。在这项研究中,我们调查了MT1和MT2敲除小鼠的视网膜色素上皮的吞噬活动的日常节律。我们的数据表明,在MT1和MT2敲除小鼠中,吞噬作用的峰值相对于野生型小鼠提前了3 h,并且在黑暗中而不是在光照后出现,尽管在24小时内平均吞噬活性三种基因型之间的时间没有变化。然而,每日吞噬节律的这种微小变化可能会对视网膜健康产生重大影响,因为敲除MT1和MT2的小鼠在视网膜色素上皮中的脂褐素积聚明显增加。

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