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Les horloges circadiennes, permettant l´anticipation des changements environnementaux cycliques, sont synchronisés par la lumière du jour via un signal lumineux à la rétine. Outre les cônes et les bâtonnets, la rétine contient des cellules ganglionnaires intrinsèquement photosensibles (ipRGCs), subdivisées en sous-types distincts exprimant le pigment mélanopsine et impliquées dans l´entrainement de l´horloge biologique à la lumière. Le système circadien est très similaire chez les animaux nocturnes et diurnes. L'objectif de cette thèse était d'étudier les propriétés morphologiques, moléculaires etphysiologiques des ipRGCs de rongeurs nocturnes (souris) et diurnes (Arvicanthis ansorgei). Ce travail révèle des morphologies comparables des différents types d´ipRGCs pour les deux espèces, mais la proportion du type M1 était plus élevée chez Arvicanthis. Des immunomarquages spécifiques des cellules ganglionnaires de la rétine ont révélé que les ipRGCs constituent une population hétérogène. Chez les deux espèces, l'expression de neurofilaments et de Brn3 différait selon le type d´ipRGC. Les propriétés physiologiques des ipRGCs étaient principalement similaires pour les deux espèces. Chez Arvicanthis, les ipRGCs de type I étaient plus sensibles à de courts éclairs lumineux. En conclusion , les ipRGCs des rongeurs nocturnes et diurnes partagent des caractéristiques communes. Cette étude est la première à décrire la sensibilité des ipRGCs a des éclairs de courte durée. De plus, ce travail étend les connaissances sur l'hétérogénéité moléculaire des différents types d´ipRGCs. / Circadian clocks permit anticipation of cyclic environmental changes and are synchronized to solar day through photic input from the retina. Besides rods and cones, the retina contains intrinsically photosensitive retinal ganglion cells (ipRGCs), consisting of distinct sub-types. IpRGCs express the photopigment melanopsin and are implicated in photoentrainment of the biological clock. Light information shapes the animal’s temporal behavior, but the circadian systems of nocturnal and diurnal animals appear to be very similar. The aim of this thesis was to investigate the morphological, molecular and physiologicalproperties of ipRGCs in nocturnal (C57BL/6 mouse) compared to diurnal (Arvicanthis ansorgei) rodents. The morphological analysis revealed comparable characteristics of the different ipRGC types in both species; however the proportion of M1 cells was higher in Arvicanthis than in mouse. Immunostaining patterns using RGC markers revealed that ipRGCs are a heterogeneous population. In both species, Brn3 and neurofilaments expression were partly distinct between the ipRGC types.The physiological properties of ipRGC types were mostly similar between the two species, but type I ipRGCs were more sensitive to short light flashes in Arvicanthis than in mouse. In conclusion, the melanopsin system of nocturnal and diurnal rodents shares many common features. Importantly, this study is the first describing responses of ipRGCs to short light flashes and the observed molecular heterogeneity extends the characterization of individual ipRGC types.

This master thesis is focused on designing a concept of a biodynamic tunable white luminaire for the interior capable of producing user defined output or simulating the conditions of natural exterior lighting. The thesis describes the physiological basis of human sensitivity to lighting and the consequences, as well as the principles of semiconductor radiation sources. Finally, it deals with methods of sensing the lighting conditions and describing the design and functions of the system elements and final implementation.

Light not only allows us to see but is also fundamental to our health and well-being. Several parameters of light exposure, such as wavelengths, intensity, and timing of exposure, all play an important role on its effects on psychophysiological functions. The way in which studies have previously quantified light (based on intensity), has been found to be inadequate since it does not consider the spectrum of light which influences non-visual effects. Among these non-visual effects, light has been found to have antidepressant effects, however, these effects remain inconsistent for non-seasonal depression and their underlying mechanisms remain elusive. The three research studies in this thesis investigated the effects of light on mood. The first study focused on the direct pathway between light and mood, aiming to predict mood outcomes based on the amount of intrinsically photosensitive retinal ganglion cells (ipRGC) stimulation from polychromatic light in healthy individuals. The second and third studies focused on the indirect pathways, exploring predictors and underlying mechanisms of mood improvements by means of sleep and circadian re-alignment in the context of non-seasonal depression. These studies explored the antidepressant mechanisms of monochromatic light therapy and predictive models of mood improvement. The results from study I (systematic review) suggest that ipRGCs may not be as involved in the mood improvement associated with polychromatic light. Drawing strong conclusions from these results are, however, cautioned. Mood metrics used across the studies were inconsistent and the light sources were not designed to maximally stimulate ipRGCs. The results from study II (open-label trial) support the notion that light therapy does have antidepressant effects in people with non-seasonal depression. The underlying mechanisms for these antidepressant effects may involve improvements in sleep initiation and daytime functioning. Individuals with difficulties with fallings asleep and waking-up may be those that respond most prominently to light therapy. The results from study III (randomized controlled trial) indicate that depression symptoms improved slightly more in the active light therapy condition as opposed to a placebo condition. Although this effect was modest across the overall group, there were considerable inter-individual variations in treatment response. The degree of improvement in mood was associated with improvement in pre-sleep thoughts and the circadian rhythmicity of skin temperature. Short REM latency and worst global subjective sleep were predictive of greater response to light therapy. Overall, further research is required to disentangle the involvement of the different photoreceptors in the mood response to polychromatic light in healthy individuals. Monochromatic light therapy for non-seasonal depression yields overall modest antidepressant effects. Clinical applications of light therapy may benefit from further research investigating differential effects in sub-groups of depression and underlying mechanisms in larger studies.

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