The mammalian retina as a clock

Tosini, Gianluca; Fukuhara, Chiaki

doi:10.1007/s00441-002-0578-z

Cited by 77 publications

(67 citation statements)

References 61 publications

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“…The first is intrinsic to the retina and is evidenced by the findings that many molecules of importance to retinal function and many retinal activities have a circadian rhythm of expression (summarized in Tosini and Fukuhara, 2002). In many of the studies, including our own, the eyes were not separated from the animal, permitting a possible centrifugal influence of the SCN on the retina.…”

Section: Possible Function Of Biological Clock Proteins In Retinal Ammentioning

confidence: 99%

“…There is solid evidence that vertebrate retinas contain one or more biological clocks (for review, see Anderson and Green, 2000;Tosini and Fukuhara, 2002). These intrinsic pacemakers control the circadian rhythmicity of certain retinal functions, such as N-acetyltransferase expression and melatonin synthesis (Besharse and Iuvone, 1983), synthesis of the cone pigment, iodopsin (Pierce et al, 1993), and outer segment disk shedding by rods (Terman et al, 1993).…”

Section: Biological Clock Genes In the Retinamentioning

confidence: 99%

“…Circadian clocks also serve to coordinate the optimal phase of internal events of various tissues and organs. In mammals the master biological clock lies in the suprachiasmatic nuclei (SCN), but there is good evidence for one or more independent clocks in the retina (Anderson and Green, 2000;Tosini and Fukuhara, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Cellular Location and Circadian Rhythm of Expression of the Biological Clock GenePeriod 1in the Mouse Retina

et al. 2003

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The cellular location and rhythmic expression of Period 1 (Per1) circadian clock gene were examined in the retina of a Per1::GFP transgenic mouse. Mouse Per1 (mPer1) RNA was localized to inner nuclear and ganglion cell layers but was absent in the outer nuclear (photoreceptor) layer. Green fluorescent protein (GFP), which was shown to colocalize with PER1 protein, was found in a few subtypes of amacrine neuron, including those containing tyrosine hydroxylase, calbindin, and calretinin, but not in cholinergic amacrine cells. A small subset of ganglion cells also contained GFP immunoreactivity (GFP-IR), but the melanopsin-containing subtype, which projects to the suprachiasmatic nuclei (SCN), lacked GFP-IR. Although the intensity of GFP-IR varied among the populations of amacrine cells at each time point that was examined, both diurnal and circadian rhythms were found for the fraction of neurons showing strong GFP-IR, with peak expression between Zeitgeber/circadian (ZT/CT) times 10 and 14. In SCNs that were examined in the same mice used for the retinal measures, the peak in GFP-IR also occurred at approximately ZT/CT 10. Our results are the first to demonstrate a circadian rhythm of a biological clock component in identified neurons of a mammalian retina.

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Section: Possible Function Of Biological Clock Proteins In Retinal Ammentioning

confidence: 99%

Section: Biological Clock Genes In the Retinamentioning

confidence: 99%

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Cellular Location and Circadian Rhythm of Expression of the Biological Clock GenePeriod 1in the Mouse Retina

et al. 2003

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“…The promoter of the Aanat gene contains an E-box sequence, which was shown to be stimulated by BMAL1/CLOCK. 87 This gene is likely regulated as well through its well-conserved CRE site, which mediates cyclic adenosine monophosphate (cAMP) activation potentially during the night, following photoreceptor depolarization. This CRE-mediated control probably works also in constant conditions because cAMP is rhythmic in constant darkness.…”

Section: Functions Controlled By the Retina Clockmentioning

confidence: 99%

The retinal clock in mammals: role in health and disease

Felder-Schmittbuhl¹,

Calligaro²,

Dkhissi-Benyahya³

2017

CPT

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Abstract:The mammalian retina contains an extraordinary diversity of cell types that are highly organized into precise circuits to perceive and process visual information in a dynamic manner and transmit it to the brain. Above this builds up another level of complex dynamic, orchestrated by a circadian clock located within the retina, which allows retinal physiology, and hence visual function, to adapt to daily changes in light intensity. The mammalian retina is a remarkable model of circadian clock because it harbors photoreception, self-sustained oscillator function, and physiological outputs within the same tissue. However, the location of the retinal clock in mammals has been a matter of long debate. Current data have shown that clock properties are widely distributed among retinal cells and that the retina is composed of a network of circadian clocks located within distinct cellular layers. Nevertheless, the identity of the major pacemaker, if any, still warrants identification. In addition, the retina coordinates rhythmic behavior by providing visual input to the master hypothalamic circadian clock in the suprachiasmatic nuclei (SCN). This light entrainment of the SCN to the light/dark cycle involves a network of retinal photoreceptor cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it was considered that these photoreceptors synchronized both retinal and SCN clocks, new data challenge this view, suggesting that none of these photoreceptors is involved in photic entrainment of the retinal clock. Because circadian organization is a ubiquitous feature of the retina and controls fundamental processes, the coherence from cell to tissue is critical for circadian functions, and disruption of retinal clock organization or its response to light can potentially have a major impact on retinal pathophysiology and vision.

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“…The duration of the daily increase in melatonin reflects the number of hours of darkness in the 24-h cycle and therefore signals the season of the year. Although local melatonin production has been demonstrated in several tissues (retina, digestive tract and testis; Tosini and Fukuhara, 2002;Messner et al, 2001;Tijmes et al, 1996;respectively), the circulating melatonin derives from the pineal organ (Lewy et al, 1980).The daily plasma melatonin rhythm depends on an intact SCN as demonstrated by its disappearance after the lesion of this nucleus (Meyer-Bernstein et al, 1999). A related finding is that a bright light pulse during dark hours quickly lowers the plasma melatonin concentration (Leproult et al, 2001).…”

Section: Melatonin As a Neuroendocrine Transducer For Circadian Rhythmsmentioning

confidence: 99%

The Circadian Timing System: Making Sense of day/night gene expression

et al. 2004

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The circadian time-keeping system ensures predictive adaptation of individuals to the reproducible 24-h day/ night alternations of our planet by generating the 24-h (circadian) rhythms found in hormone release and cardiovascular, biophysical and behavioral functions, and others. In mammals, the master clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. The molecular events determining the functional oscillation of the SCN neurons with a period of 24-h involve recurrent expression of several clock proteins that interact in complex transcription/translation feedback loops. In mammals, a glutamatergic monosynaptic pathway originating from the retina regulates the clock gene expression pattern in the SCN neurons, synchronizing them to the light:dark cycle. The emerging concept is that neural/humoral output signals from the SCN impinge upon peripheral clocks located in other areas of the brain, heart, lung, gastrointestinal tract, liver, kidney, fibroblasts, and most of the cell phenotypes, resulting in overt circadian rhythms in integrated physiological functions. Here we review the impact of day/night alternation on integrated physiology; the molecular mechanisms and input/output signaling pathways involved in SCN circadian function; the current concept of peripheral clocks; and the potential role of melatonin as a circadian neuroendocrine transducer.

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The mammalian retina as a clock

Cited by 77 publications

References 61 publications

Cellular Location and Circadian Rhythm of Expression of the Biological Clock GenePeriod 1in the Mouse Retina

Cellular Location and Circadian Rhythm of Expression of the Biological Clock GenePeriod 1in the Mouse Retina

The retinal clock in mammals: role in health and disease

The Circadian Timing System: Making Sense of day/night gene expression

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