Project description:The sensation of light is initiated in photoreceptor cells by the photoisomerization of a chromophore molecule from 11-cis to all-trans retinal. Continuous visual perception requires recycling of the spent chromophore back to the 11-cis form through the visual cycle, a series of reactions in the retinal pigmented epithelium (RPE). Light-driven chromophore consumption by photoreceptors is greater in daytime compared to night time, suggesting that correspondingly higher activity of the visual cycle may be required. On the other hand, as rod photoreceptors are saturated in bright light, the continuous turnover of their chromophore through the visual cycle during daytime would unnecessarily utilize precious energy and produce toxic byproducts. Here, we sought to determine whether the recycling of chromophore and the dark adaptation of rods is regulated by the circadian clock and light exposure. We demonstrate that in melatonin-proficient C3H/f+/+ mice, rod dark adaptation is slower during the day or after light exposure. This surprising daytime downregulation of the RPE visual cycle was further demonstrated by gene analysis, which revealed light-driven reduction in the expression of Rpe65, which encodes a key enzyme of the RPE visual cycle. In contrast, rods in melatonin-deficient strains (C57BL6/J and 129/Sv) were not affected by this daily visual cycle modulation. Our results demonstrate that the circadian clock and light exposure regulate the recycling of chromophore in the RPE visual cycle. This daily modulation of rod dark adaptation is mediated by melatonin and could potentially protect the retina from light-induced damage during the day.
Project description:The sensation of light is initiated in photoreceptor cells by the photoisomerization of a chromophore molecule from 11-cis to all-trans retinal. Continuous visual perception requires recycling of the spent chromophore back to the 11-cis form through the visual cycle, a series of reactions in the retinal pigmented epithelium (RPE). Light-driven chromophore consumption by photoreceptors is greater in daytime compared to night time, suggesting that correspondingly higher activity of the visual cycle may be required. On the other hand, as rod photoreceptors are saturated in bright light, the continuous turnover of their chromophore through the visual cycle during daytime would unnecessarily utilize precious energy and produce toxic byproducts. Here, we sought to determine whether the recycling of chromophore and the dark adaptation of rods is regulated by the circadian clock and light exposure. We demonstrate that in melatonin-proficient C3H/f+/+ mice, rod dark adaptation is slower during the day or after light exposure. This surprising daytime downregulation of the RPE visual cycle was further demonstrated by gene analysis, which revealed light-driven reduction in the expression of Rpe65, which encodes a key enzyme of the RPE visual cycle. In contrast, rods in melatonin-deficient strains (C57BL6/J and 129/Sv) were not affected by this daily visual cycle modulation. Our results demonstrate that the circadian clock and light exposure regulate the recycling of chromophore in the RPE visual cycle. This daily modulation of rod dark adaptation is mediated by melatonin and could potentially protect the retina from light-induced damage during the day. mRNA-seq of murine eyes (lens removed) in objective day (OD) vs. subjective day (SD) conditions (2 biological replicates per condition). Each biological replicate consisted of 4 eyes (from 1 female and 1 male).
Project description:Using larval zebrafish as a model system, we applied a genome-wide transcriptome approach that allowed us to investigate circadian gene expression that can be associated with various tissues and cell types. Our analysis of circadian gene regulatory network revealed a general principle: circadian clock controls diverse aspects of circadian physiology through transcriptional cascade of transcription factors (TFs). As a proof of this principle, we focused on microphthalmia-associated transcription factor a (mitfa), a dark-induced TF controlling melanogenesis in melanocytes. We demonstrated experimentally that there is a circadian rhythm of melanin synthesis mediated by mitfa. The circadian rhythm of mitfa is in turn driven by both endogenous clock and external light/dark cycle. The circadian rhythm of melanin synthesis may play an important role in zebrafish’s adaptation to daily cycle of lighting condition in the environment.
Project description:Pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. However, the enzyme responsible for the oxidation of 11-cis-retinol remains unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10), upregulated in rod/cone hybrid retinas and expressed abundantly in Müller cells, is the enzyme that drives this reaction. We created mice lacking RDH10 either in cone photoreceptors, Müller cells, or the entire retina. In vivo electroretinography and transretinal recordings revealed normal cone photoresponses in all RDH10-deficient mouse lines. Notably, their cone-driven dark adaptation both in vivo and in isolated retina was unaffected, indicating that RDH10 is not required for the function of the retina visual cycle. We also generated transgenic mice expressing RDH10 ectopically in rod cells. However, rod dark adaptation was unaffected by the expression of RDH10 and transgenic rods were unable to use cis-retinol for pigment regeneration. We conclude that RDH10 is not the dominant retina 11-cis-RDH, leaving its primary function in the retina unknown.
Project description:Circadian clocks drive ~24 hr rhythms in tissue physiology. They rely on transcriptional/translational feedback loops driven by interacting networks of clock complexes.To gain insights into the role of the mammary clock, circadian time-series microarrays were performed to identify rhythmic genes in vivo. Breast tissues were isolated at 4 hr intervals for two circadian (24 hourly) cycles, from mice kept under constant darkness to avoid any light- or dark-driven genes.
Project description:We utilized the Nematostella vectensis to quantify gene expression differences and loss during light:dark cycling and immediately after light cue removal through comparisons of 136 transcriptomes Organismal responses to light:dark cycles can result from two general processes: (i) direct response to light or (ii) a free-running rhythm (i.e., a circadian clock). Previous research in cnidarians has shown that candidate circadian clock genes have rhythmic expression in the presence of diel lighting, but these oscillations appear to be lost quickly after removal of the light cue. Here, we measure whole-organism gene expression changes in 136 transcriptomes of the sea anemone Nematostella vectensis, entrained to a light:dark environment and immediately following light cue removal to distinguish two broadly defined responses in cnidarians: light entrainment and circadian regulation. Direct light exposure resulted in significant differences in expression for hundreds of genes, including more than 200 genes with rhythmic, 24-hour periodicity. Removal of the lighting cue resulted in the loss of significant expression for 80% of these genes after one day, including most of the hypothesized cnidarian circadian genes. Further, 70% of these candidate genes were phase shifted. Most surprisingly, thousands of genes, some of which are involved in oxidative stress, DNA damage response, and chromatin modification, had significant differences in expression in the 24 hours following light removal, suggesting that loss of the entraining cue may induce a cellular stress response. Together, our findings suggest that a majority of genes with significant differences in expression for anemones cultured under diel lighting are largely driven by the primary photoresponse rather than a circadian clock when measured at the whole animal level. These results provide context for the evolution of cnidarian circadian biology and help to disassociate two commonly confounded factors driving oscillating phenotypes.
Project description:Tikidji-Hamburyan2018 - Rod phototransduction
under strong illumination
This model is described in the article:
Rods progressively escape
saturation to drive visual responses in daylight
conditions.
Tikidji-Hamburyan A, Reinhard K,
Storchi R, Dietter J, Seitter H, Davis KE, Idrees S, Mutter M,
Walmsley L, Bedford RA, Ueffing M, Ala-Laurila P, Brown TM, Lucas
RJ, Münch TA.
Nat Commun 2017 Nov; 8(1): 1813
Abstract:
Rod and cone photoreceptors support vision across large
light intensity ranges. Rods, active under dim illumination,
are thought to saturate at higher (photopic) irradiances. The
extent of rod saturation is not well defined; some studies
report rod activity well into the photopic range. Using
electrophysiological recordings from retina and dorsal lateral
geniculate nucleus of cone-deficient and visually intact mice,
we describe stimulus and physiological factors that influence
photopic rod-driven responses. We find that rod contrast
sensitivity is initially strongly reduced at high irradiances,
but progressively recovers to allow responses to moderate
contrast stimuli. Surprisingly, rods recover faster at higher
light levels. A model of rod phototransduction suggests that
phototransduction gain adjustments and bleaching adaptation
underlie rod recovery. Consistently, exogenous chromophore
reduces rod responses at bright background. Thus, bleaching
adaptation renders mouse rods responsive to modest contrast at
any irradiance. Paradoxically, raising irradiance across the
photopic range increases the robustness of rod responses.
This model is hosted on
BioModels Database
and identified by:
MODEL1710030000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
Project description:Anopheles gambiae, the primary African malarial mosquito, exhibits numerous behaviors that are under diel and circadian control, including locomotor activity, swarming, mating, host seeking, eclosion, egg laying and sugar feeding. However, little has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is globally regulated by diel and circadian mechanisms, we have undertaken a DNA microarray analysis of A. gambiae head and bodies under 12:12 light:dark cycle (LD) and constant dark (DD, free-running) conditions. Zeitgeber Time (ZT) with ZT12 defined as time of lights OFF under the light:dark cycle, and ZT0 defined as end of the dawn transition. Circadian Time (CT) with CT0 defined as subjective dawn, inferred from ZT0 of the previous light:dark cycle.
Project description:The mosquito Ae. aegypti is responsible for the transmission of many diseases including yellow fever and Dengue fever. This species exhibits many behaviors that are under diel and circadian control. However, there has been little reporting on gene expression rhythmicity. To study how gene expression is globally regulated by diel and circadian mechanisms, we have undertaken a DNA microarray analysis of Ae. aegypti head and bodies under 12:12 light:dark cycle (LD) and constant dark (DD, free-running) conditions. Zeitgeber Time (ZT) with ZT12 defined as the initiation of the one hour dusk period under the light:dark cycle, and ZT0 defined as beginning of the one hour dawn period. Circadian Time (CT) with CT0 defined as subjective dawn, inferred from ZT0 of the previous light:dark cycle.