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  • Location : Bron, France
Last update 2019-05-02 16:54:14.789

Ouria Dkhissi-Benyahya PhD Neurosciences

Course and current status

My scientific project has focused on circadian photoreception and the entrainment by light of the central clock. 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 that 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), (3) a new type of "dichromate" cone in rodents (Coexpression of two opsins in the same cone (Lukats et al., 2002) and (4) the demonstration of a new type of melanopsin cone in humans (Dkhissi-Benyahya et al., IOVS, 2006). 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). I then 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., Neuron, 2007; Dollet et al., Chronobiol Int 2010).In 2006, We demonstrated an additional regulatory feedback loop involving the clock gene Bmal1 and the Peroxisome Proliferator Activated Receptor-a (PPARa) in peripheral clocks (Canaple et al., Mol Endocrinol 2006) and participate to the development of new mouse model that allow in vivo imaging of peripheral clocks (Canaple et al. Cell Mol Life Sci. 2018). My current research goal aims to understand the molecular mechanisms underlying rhythm generation in the retinal clock and how light entrains this clock. I showed that the retinal clock is composed of a network of clocks in which melanopsin is playing an important role in light response (Dkhissi-Benyahya et al., Cell Mol Life Sci, 2013). The consequences of pathologies on the functioning and light response of the retinal clock are also studied (Lahouaoui et al., PlosOne2014, Mol Vision2016, Felder-Schmittbuhl et al., Chronobiol and Therapy 2017, IOVS 2018). Recently, I was involved in an extensive study of rhythmic gene regulation in the non-human primate (Mure et al., Science 2018). I showed that the retinal clock is composed of a network of clocks in which melanopsin is playing an important role in retinal clock mechanism (Dkhissi-Benyahya et al., Cell Mol Life Sci, 2013) and highlighted an indispensable role of rods in the phase shift of the retinal clock (Calligaro et al., Plos Biol 2019). I have a broad background in molecular, cellular, anatomical and behavioral approaches and light manipulations in rodent models.

I participated in over 50 conferences, 16 as invited speaker and in the organisation of  international and national conferences and PI or coinvestigator of several national, european and international funding (Biomed2, FP5-OldClock, FP6-EUClock, ACI, ACT, ANR Neuro, ANR Blanc, ANR TECSAN, CMIRA, RETINA-France, USIAS).

I have been member of the National Commission for University (69-Neurosciences), administrative board of the “Société Francophone de Chronobiologie” (SFC), elected the general secretary of SFC. I am currently board member of the Doctoral School Neurosciences and Cognition of Lyon and member of the editorial board of “Journal of Circadian Rhythms” and” Data Set papers on Medecine”. I am involved in teaching chronobiology at master level in Lyon and in training master and PhD students from Morroco (EuroMediterranean Master of Neurosciences and Biotechnology, Marrakech)

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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