Circadian Disruption in Glaucoma: Causes, Consequences, and Countermeasures.

This review explores the intricate relationship between glaucoma and circadian rhythm disturbances. As a principal organ for photic signal reception and transduction, the eye plays a pivotal role in coordinating the body's circadian rhythms through specialized retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs). These cells are critical in transmitting light signals to the suprachiasmatic nucleus (SCN), the central circadian clock that synchronizes physiological processes to the 24-hour light-dark cycle. The review delves into the central circadian body clock, highlighting the importance of the retino-hypothalamic tract in conveying light information from the eyes to the SCN. It underscores the role of melanopsin in ipRGCs in absorbing light and initiating biochemical reactions that culminate in the synchronization of the SCN's firing patterns with the external environment. Furthermore, the review discusses local circadian rhythms within the eye, such as those affecting photoreceptor sensitivity, corneal thickness, and intraocular fluid outflow. It emphasizes the potential of optical coherence tomography (OCT) in studying structural losses of RGCs in glaucoma and the associated circadian rhythm disruption. Glaucomatous retinal damage is identified as a cause of circadian disruption, with mechanisms including oxidative stress, neuroinflammation, and direct damage to RGCs. The consequences of such disruption are complex, affecting systemic and local circadian rhythms, sleep patterns, mood, and metabolism. Countermeasures, with implications for glaucoma management, are proposed that focus on strategies to improve circadian health through balanced melatonin timing, daylight exposure, and potential chronotherapeutic approaches. The review calls for further research to elucidate the mechanisms linking glaucoma and circadian disruption and to develop effective interventions to address this critical aspect of the disease.