Circadian Signaling in the Retina
Simply put, our research aims to understand how we see during the day and night. Our visual system is remarkable in that it can operate under the bright midday sun, at night under starlight, and at all times in between when ambient light intensity varies by more than 10 billion fold. The mechanisms responsible for this remarkable adaptation are known to primarily originate in the eye and more specifically in its sensory part, the retina. Adaptation to the daily changes in ambient light intensity in the retina depends on a specific functional architecture, including 2 types of photoreceptors, rods and cones, and a wide variety of neuronal mechanisms encompassing both adaptive mechanisms driven by ambient light and endogenous mechanisms, such as circadian clocks. The main property of circadian clocks is that they are self-sustained in nature, and therefore they function even in the absence of time cues, such as in constant conditions (i.e. constant darkness) with a period of approximately 24 h, hence the term circa-dian (from the Latin circa dies, which translates into “about one day”). Circadian clocks in the retina keep track of the highly predictable daily changes in the ambient light intensity, thus helping the retina to anticipate the abrupt changes in lighting conditions at transition times (i.e. dawn and dusk) and optimize retinal processing for high-acuity low-sensitivity daytime vision or low-acuity high-sensitivity nighttime vision. Genetic dysfunction of the retinal clocks or of circadian signaling in the retina produces marked deficits in retinal responses to light and compromises retinal cell viability. Thus, functional circadian clocks are essential for normal maintenance and function of the retina.
Our long-term goal is to understand how circadian clocks in the retina modulate retinal function on a daily basis, and why clock malfunction impinges on information processing and cell viability. We expect that our work will bring us closer to fully understand why circadian timing is so critical in the retina. We also expect that understanding how circadian clocks control neuronal activity and functional pathways in the retina will be of great benefit towards our understanding of the general rules governing circadian clock function and neuroplasticity in the central nervous system.
Working model and current projects in the lab.
A major hypothesis in our laboratory is that clocks exist in most retinal cell types, and each clock cell type controls specific aspects of retinal function through an exclusive clock pathway. The figure shows a simplified schematic representation of the anatomy of the vertebrate retina with a hypothetical clock in a cone photoreceptor that controls the release of an effector, which modulates the activity of a bipolar cell and thereby that of a retinal circuit. This clock pathway may have an important impact on cell viability and some aspects of vision. We anticipate that a detailed identification of the circadian clock cells in the retina, together with the identification of retinal neurons and functional pathways that are controlled by the retinal clocks, will help us understand how the retina processes visual information during day and night, and why clock dysfunction contributes to retinal degeneration.