The proposed study is a project based on the collaboration between Drs Kleinlogel and Adamantidis that are experts in vision/optogenetics and sleep regulation, respectively, and Dr. Mure, which has longstanding expertise in non-visual photoreception. Synergizing our fields will kick-start a new research direction into non-circadian regulation of sleep, mood, cognition, and potentially other physiological effects directly mediated by light.
In modern societies, humans are exposed to artificial lighting and shift work, misaligning their circadian clock and leading to sleep disruption. Sleep disruption is a hallmark of several disorders including neurodegeneration, depression, and cardiovascular disease. The multidisciplinary project, combining retina biology, sleep research, and biotechnology, opens the path to a better understanding of how light acutely affects sleep and alertness. It will have a seminal impact on preventing and managing an increasing epidemic of chronic diseases triggered by aberrant light exposure and sleep disruption. The proposal also includes a very specific translational approach, namely the evaluation of an optogenetic treatment of sleep disorders in retinal degeneration patients, rendering the project directly relevant to human health.
Light influences humans at all levels – it sets our circadian clock, controls our hormones, sleep, alertness, mood, and adapts our whole physiology to the day-night cycle. However, in modern societies, continuous artificial lighting leads to chronic disruption of the circadian and sleep-wake cycles, either predisposing to or directly inducing several diseases including neurodegeneration, major depressive disorder, and seasonal affective disorder.
Light can modulate the sleep-wake cycle either indirectly through its effect of light on the phase of the circadian clock or directly via retinal ganglion cell projections to hypothalamic and thalamic nuclei implicated in the regulation of sleep and alertness. The frequent appearance of sleep disorders in retinal degeneration patients with a functioning circadian clock support the assumption that vigilance states are directly regulated by retinal input.
While retinal light entrainment of the circadian clock is well understood, the non-circadian, direct effects of light on alertness remain elusive. Understanding how light directly affects sleep-wake controlling nuclei will have a seminal impact on preventing and managing an increasing epidemic of chronic diseases that are related to aberrant light exposure and sleep disruption.
The consortium proposes an interdisciplinary approach, coupling cutting-edge neuroscience and biotechnology methods to identify retinal ganglion cell pathways to sleep-wake controlling brain centers and to test their functional effects on vigilance states. In a translational approach, they will test the possibility to optogenetically revert the negative effects of retinal degeneration on the direct sleep-wake pathways and try to find the human ganglion cell correlates of direct sleep-wake regulation.
This study is topical in modern times dominated by artificial lighting and will constitute the first step towards a systematic dissection of the mechanisms and pathways supporting the direct effects of light on sleep-wake regulation. The new insights will pave the way to tailored therapies counteracting diseases due to aberrant light exposure.