Sleep deprivation, a growing concern in modern society, affects a significant portion of the global population, with major health implications (Sang et al., 2023; Li et al., 2022). Recent studies, including those by the Centers for Disease Control and Prevention and the Chinese Sleep Research Association, highlight a widespread trend of insufficient sleep (Watson et al., 2015). This trend has serious repercussions, notably in ocular health. While chronic sleep deprivation (CSD) is linked to various eye diseases (Waller et al., 2008; Li et al., 2018; Huang et al., 2022) such as dry eye syndrome, (Karaca et al., 2019) glaucoma, (Bendel et al., 2008) and diabetic retinopathy, (Wu et al., 2018; Liu et al., 2020) its specific impact on retinal health, particularly in terms of structure and function, is not well understood.

Central to our study is the circadian rhythm, the intrinsic 24-h cycle regulating behavioral and physiological processes, (Bass and Takahashi, 2010) which is initiated in the retina. Intrinsically photosensitive retinal ganglion cells detect light changes (van Diepen et al., 2021; Güler et al., 2008) and relay signals to the suprachiasmatic nucleus (SCN) in the hypothalamus, the central circadian system's pacemaker (Moore and Eichler, 1972; Hastings et al., 2018). The SCN coordinates circadian activities across different organs, (Dibner et al., 2010; Wang et al., 2021) including the retina, which has its own autonomous circadian rhythm (Wang et al., 2021; Ko, 2020; Chaurasia et al., 2006; Sandu et al., 2011; Ye et al., 2023). This rhythm influences key retinal processes such as dopamine synthesis, (Doyle et al., 2002) pH regulation, (Dmitriev and Mangel, 2001) and visual protein transcription, (von Schantz et al., 1999) crucial for maintaining visual function and cell health. Previous studies have shown that the retina exhibits robust transcriptome rhythmicity (Wang et al., 2021). Diabetes significantly alters the transcriptome signature of the circadian transcriptome in the retina (Ye et al., 2023; Busik et al., 2009; Vancura et al., 2021; Lahouaoui et al., 2016).

Despite known impacts of sleep deprivation on aspects like retinal thickness (Sahbaz et al., 2020) and electrophysiological activity, (Kawasaki et al., 2018; Reist et al., 1995) the molecular mechanisms underlying its effect on the retinal circadian rhythm remain poorly explored. Our study hypothesizes that CSD adversely affects these crucial circadian functions, leading to structural and functional retinal changes. Through an in-depth analysis of the circadian transcriptome profiles in retinas subjected to 4 weeks of CSD in a mouse model, we uncover significant disruptions in the retinal circadian rhythm and pathological changes, including increased ROS accumulation. These findings not only emphasize the importance of regular sleep for retinal health but also pave the way for novel approaches in treating sleep deprivation-related retinal disorders.