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Last update 2011-07-18 12:18:21.285

Ouria Dkhissi-Benyahya PhD Neurosciences

Course and current status

I have made major contributions to the field of circadian photoreception and in particular on the mechanisms of photon integration in the suprachiasmatic nucleus (SCN) by first developing a method of quantification of early genes (c-fos) expression in the site of the endogenous clock, the SCN. I have shown by this cellular approach that the temporal integration of photons extends on a scale of extremely long time (a few seconds to 1 hour) and that the site of integration is at the level of the SCN (Dkhissi-Benyahya et al., 2000). This cellular approach has allowed me to demonstrate a reduction of the effect of light on the photic induction of c-fos, together with an effect on the secretion of melatonin, during normal and accelerated aging in a primate (Aujard et al., 2001). In parallel, I was able to develop international collaborations with our partners in the network Biomed, international experts in the field of photoreceptor characterization in rodents and primates. In collaboration with A. Szel (Budapest) and W. Degrip (Nijmegen), I highlighted 1) the presence of SW cones in a prosimian primate, previously considered as absent in this group (Dkhissi-Benyahya et al., 2001) 2) cell markers common to photoreceptors in major groups of primates, including humans (Chiquet et al., 2002; Chiquet et al., 2005) and (3) a new type of "dichromate" cone in rodents (Coexpression of two opsins in the same cone (Lukats et al., 2002) . In recent publications, I established the concept of response domains of different photoreceptors in circadian photoreception and modelled the relative contributions of different types of photoreceptors (Dkhissi-Benyahya et al., 2007). We proposed in 2008 that the classical view of glaucoma as pathology unique to the visual system should be extended to include anatomical and functional alterations of the circadian timing system (Drouyer et al., 2008). In 2006, We demonstrated in collaboration with L. Canaple (E.N.S., Lyon) an additional regulatory feedback loop involving the clock gene Bmal1 and the Peroxisome Proliferator Activated Receptor-a (PPARa) in peripheral clocks (Canaple et al., 2006). During my career I have published 21 articles in international journals, including Neuron, Journal of Neuroscience, Molecular Endocrinology, PlosOne.

I was co-investigator in several national (INSERM-PECO, ACI, ACT, Rhones-Alpes), european (Biomed2, FP5-OldClock, FP6-EUClock) and international (Mira, Volubilis) projects and principal investigator  in national fundings (Retina France 2008 and 2009).

I have participated in over 40 conferences and participated in the organisation of 3 international and national conferences. I’m an elected member of the administrative board of the “Société Francophone de Chronobiologie”, which regroup all the French-spoken chronobiologists over the world. In 2010, I was elected as the general secretary of this scientific society. I’m involved in teaching chronobiology at master level in different universities in France (Lyon, Besanson, Ecole Normale Supérieure) and I’m currently involved in a join PhD “co-tutelle” in collaboration with the University of Marrakech. I’m a part of the master committee at the University of Lyon.

Scientific summary

The vertebrate retina is both a sensory organ and an endogenous circadian clock. As a circadian clock, the retina expresses many physiological or functional circadian rhythms including rod outer segment disc shedding and phagocytosis by the retinal pigment epithelium, expression of immediate early genes and opsin genes in photoreceptors, N-acetyltransferase expression and dopamine/melatonin synthesis. Although these events are critical for retinal functions, it remains unclear how the mammalian retinal circadian clock controls ocular and central physiological rhythmicity.

The central circadian clock, localized in the suprachiasmatic nucleus (SCN) of the hypothalamus is synchronized by the environmental 24h light/dark cycle via the retina. This process involves photon capture by retinal photopigments (rods, cones and melanopsin-expressing ganglion cells). The endogenous functioning of circadian clocks involves an integrated network of interacting self-sustained clock genes in transcriptional-translational feedback loops.

It is now clearly established that the absence of one or several photoreceptors leads to behavioral deficits (photic entrainment, phase shifting response to light, period length in dim light) suggesting alterations at several levels of functioning of the circadian timing system: retina, and/or central clock. Because circadian organization is a ubiquitous feature of the retina and controls fundamental pathways, disruption of retinal clock organization can potentially have a major impact on visual functions. In humans, several retinal pathologies are characterized by degeneration of photoreceptors that receive and integrate light signals from the environment. These ocular diseases represent major causes of blindness that impact on vision but also lead to a decrease or loss of the photic input to the circadian system.

My project aims to determine whether the absence of a specific photoreceptor class (melanopsin) can contribute to the dysfunction of the retinal and/or the central clocks. The functional and physiological disorders of the retinal clock is explored by coupling complementary approaches ex vivo, in vivo and in vitro in several critical mouse models. 

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