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1.
Hughes S Welsh L Katti C González-Menéndez I Turton M Halford S Sekaran S Peirson SN Hankins MW Foster RG 《PloS one》2012,7(4):e34531
Photosensitive retinal ganglion cells (pRGCs) respond to light from birth and represent the earliest known light detection system to develop in the mouse retina. A number of morphologically and functionally distinct subtypes of pRGCs have been described in the adult retina, and have been linked to different physiological roles. We have previously identified two distinct isoforms of mouse melanopsin, Opn4L and Opn4S, which are generated by alternate splicing of the Opn4 locus. These isoforms are differentially expressed in pRGC subtypes of the adult mouse retina, with both Opn4L and Opn4S detected in M1 type pRGCs, and only Opn4L detected in M2 type pRGCs. Here we investigate the developmental expression of Opn4L and Opn4S and show a differential profile of expression during postnatal development. Opn4S mRNA is detected at relatively constant levels throughout postnatal development, with levels of Opn4S protein showing a marked increase between P0 and P3, and then increasing progressively over time until adult levels are reached by P10. By contrast, levels of Opn4L mRNA and protein are low at birth and show a marked increase at P14 and P30 compared to earlier time points. We suggest that these differing profiles of expression are associated with the functional maturation of M1 and M2 subtypes of pRGCs. Based upon our data, Opn4S expressing M1 type pRGCs mature first and are the dominant pRGC subtype in the neonate retina, whereas increased expression of Opn4L and the maturation of M2 type pRGCs occurs later, between P10 and P14, at a similar time to the maturation of rod and cone photoreceptors. We suggest that the distinct functions associated with these cell types will develop at different times during postnatal development. 相似文献
2.
3.
Stuart N. Peirson Stephanie Halford Russell G. Foster 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2009,364(1531):2849-2865
Circadian rhythms are endogenous 24 h cycles that persist in the absence of external time cues. These rhythms provide an internal representation of day length and optimize physiology and behaviour to the varying demands of the solar cycle. These clocks require daily adjustment to local time and the primary time cue (zeitgeber) used by most vertebrates is the daily change in the amount of environmental light (irradiance) at dawn and dusk, a process termed photoentrainment. Attempts to understand the photoreceptor mechanisms mediating non-image-forming responses to light, such as photoentrainment, have resulted in the discovery of a remarkable array of different photoreceptors and photopigment families, all of which appear to use a basic opsin/vitamin A-based photopigment biochemistry. In non-mammalian vertebrates, specialized photoreceptors are located within the pineal complex, deep brain and dermal melanophores. There is also strong evidence in fish and amphibians for the direct photic regulation of circadian clocks in multiple tissues. By contrast, mammals possess only ocular photoreceptors. However, in addition to the image-forming rods and cones of the retina, there exists a third photoreceptor system based on a subset of melanopsin-expressing photosensitive retinal ganglion cells (pRGCs). In this review, we discuss the range of vertebrate photoreceptors and their opsin photopigments, describe the melanopsin/pRGC system in some detail and then finally consider the molecular evolution and sensory ecology of these non-image-forming photoreceptor systems. 相似文献
4.
Circadian rhythms in mammals are adjusted daily to the environmental day/night cycle by photic input via the retinohypothalamic tract (RHT). Retinal ganglion cells (RGCs) of the RHT constitute a separate light‐detecting system in the mammalian retina used for irradiance detection and for transmission to the circadian system and other non‐imaging forming processes in the brain. The RGCs of the RHT are intrinsically photosensitive due to the expression of melanopsin, an opsin‐like photopigment. This notion is based on anatomical and functional data and on studies of mice lacking melanopsin. Furthermore, heterologous expression of melanopsin in non‐neuronal mammalian cell lines was found sufficient to render these cells photosensitive. Even though solid evidence regarding the function of melanopsin exists, little is known about the regulation of melanopsin gene expression. Studies in albino Wistar rats showed that the expression of melanopsin is diurnal at both the mRNA and protein levels. The diurnal changes in melanopsin expression seem, however, to be overridden by prolonged exposure to light or darkness. Significant increase in melanopsin expression was observed from the first day in constant darkness and the expression continued to increase during prolonged exposure in constant darkness. Prolonged exposure to constant light, on the other hand, decreased melanopsin expression to an almost undetectable level after 5 days of constant light. The induction of melanopsin by darkness was even more pronounced if darkness was preceded by light suppression for 5 days. These observations show that dual mechanisms regulate melanopsin gene expression and that the intrinsic light‐responsive RGCs in the albino Wistar rat adapt their expression of melanopsin to environmental light and darkness. 相似文献
5.
Hannibal J 《Chronobiology international》2006,23(1-2):159-166
Circadian rhythms in mammals are adjusted daily to the environmental day/night cycle by photic input via the retinohypothalamic tract (RHT). Retinal ganglion cells (RGCs) of the RHT constitute a separate light-detecting system in the mammalian retina used for irradiance detection and for transmission to the circadian system and other non-imaging forming processes in the brain. The RGCs of the RHT are intrinsically photosensitive due to the expression of melanopsin, an opsin-like photopigment. This notion is based on anatomical and functional data and on studies of mice lacking melanopsin. Furthermore, heterologous expression of melanopsin in non-neuronal mammalian cell lines was found sufficient to render these cells photosensitive. Even though solid evidence regarding the function of melanopsin exists, little is known about the regulation of melanopsin gene expression. Studies in albino Wistar rats showed that the expression of melanopsin is diurnal at both the mRNA and protein levels. The diurnal changes in melanopsin expression seem, however, to be overridden by prolonged exposure to light or darkness. Significant increase in melanopsin expression was observed from the first day in constant darkness and the expression continued to increase during prolonged exposure in constant darkness. Prolonged exposure to constant light, on the other hand, decreased melanopsin expression to an almost undetectable level after 5 days of constant light. The induction of melanopsin by darkness was even more pronounced if darkness was preceded by light suppression for 5 days. These observations show that dual mechanisms regulate melanopsin gene expression and that the intrinsic light-responsive RGCs in the albino Wistar rat adapt their expression of melanopsin to environmental light and darkness. 相似文献
6.
Non-image related responses to light, such as the synchronization of circadian rhythms to the day/night cycle, are mediated by classical rod/cone photoreceptors and by a small subset of retinal ganglion cells that are intrinsically photosensitive, expressing the photopigment, melanopsin. This raises the possibility that the melanopsin cells may be serving as a conduit for photic information detected by the rods and/or cones. To test this idea, we developed a specific immunotoxin consisting of an anti-melanopsin antibody conjugated to the ribosome-inactivating protein, saporin. Intravitreal injection of this immunotoxin results in targeted destruction of melanopsin cells. We find that the specific loss of these cells in the adult mouse retina alters the effects of light on circadian rhythms. In particular, the photosensitivity of the circadian system is significantly attenuated. A subset of animals becomes non-responsive to the light/dark cycle, a characteristic previously observed in mice lacking rods, cones, and functional melanopsin cells. Mice lacking melanopsin cells are also unable to show light induced negative masking, a phenomenon known to be mediated by such cells, but both visual cliff and light/dark preference responses are normal. These data suggest that cells containing melanopsin do indeed function as a conduit for rod and/or cone information for certain non-image forming visual responses. Furthermore, we have developed a technique to specifically ablate melanopsin cells in the fully developed adult retina. This approach can be applied to any species subject to the existence of appropriate anti-melanopsin antibodies. 相似文献
7.
Jens Hannibal MD PhD Dr. Sci 《Chronobiology international》2006,23(1):159-166
Circadian rhythms in mammals are adjusted daily to the environmental day/night cycle by photic input via the retinohypothalamic tract (RHT). Retinal ganglion cells (RGCs) of the RHT constitute a separate light-detecting system in the mammalian retina used for irradiance detection and for transmission to the circadian system and other non-imaging forming processes in the brain. The RGCs of the RHT are intrinsically photosensitive due to the expression of melanopsin, an opsin-like photopigment. This notion is based on anatomical and functional data and on studies of mice lacking melanopsin. Furthermore, heterologous expression of melanopsin in non-neuronal mammalian cell lines was found sufficient to render these cells photosensitive. Even though solid evidence regarding the function of melanopsin exists, little is known about the regulation of melanopsin gene expression. Studies in albino Wistar rats showed that the expression of melanopsin is diurnal at both the mRNA and protein levels. The diurnal changes in melanopsin expression seem, however, to be overridden by prolonged exposure to light or darkness. Significant increase in melanopsin expression was observed from the first day in constant darkness and the expression continued to increase during prolonged exposure in constant darkness. Prolonged exposure to constant light, on the other hand, decreased melanopsin expression to an almost undetectable level after 5 days of constant light. The induction of melanopsin by darkness was even more pronounced if darkness was preceded by light suppression for 5 days. These observations show that dual mechanisms regulate melanopsin gene expression and that the intrinsic light-responsive RGCs in the albino Wistar rat adapt their expression of melanopsin to environmental light and darkness. 相似文献
8.
Circadian rhythms are an essential property of life on Earth. In mammals, these rhythms are coordinated by a small set of neurons, located in the suprachiasmatic nuclei (SCN). The environmental light/dark cycle synchronizes (entrains) the SCN via a distinct pathway, originating in a subset of photosensitive retinal ganglion cells (pRGCs) that utilize the photopigment melanopsin (OPN4). The pRGCs are also innervated by rods and cones and, so, are both endogenously and exogenously light sensitive. Accumulating evidence has shown that the circadian system is sensitive to ultraviolet (UV), blue, and green wavelengths of light. However, it was unclear whether colour perception itself can help entrain the SCN. By utilizing both behavioural and electrophysiological recording techniques, Walmsley and colleagues show that multiple photic channels interact and enhance the capacity of the SCN to synchronize to the environmental cycle. Thus, entrainment of the circadian system combines both environmental irradiance and colour information to ensure that internal and external time are appropriately aligned.Light is sensed by three classes of retinal photoreceptors. In the outer retina, light is detected by rod and cone photoreceptors; in the inner retina a small number of photosensitive retinal ganglion cells (pRGCs) express the photopigment melanopsin, which confers photosensitivity to these neurons. The signals derived from the various photoreceptors are important for visual and nonvisual tasks. The generation of visual images is primarily a function of the classical rod and cone photoreceptors, while the classical photoreceptors together with melanopsin are involved in nonvisual tasks, such as pupillary reflexes and the synchronization of our circadian clock to the environmental light-dark cycle. The discovery of non-rod, non-cone photoreceptors [1] and the demonstration that they utilize the photopigment melanopsin [2] led to the general and unfortunate notion that melanopsin is the major—if not the only—photopigment that contributes to photoentrainment and that this sensory task is monochromatic, with no role for colour discrimination. The article of Walmsley et al. [3] addresses this misconception and presents evidence for a role for colour detection in photoentrainment.These findings are in accordance with recent publications indicating that not only melanopsin but also other photopigments contribute to entrainment [4–9]. The consensus from these studies is that rods are most important for photoentrainment at low light intensities; cone photoreceptors transduce light information to the suprachiasmatic nuclei (SCN) at intermediate and high irradiances and are able to detect sudden changes in light intensity, whilst melanopsin detects light at high irradiances and may be of specific importance for the integration of light information over longer periods of time.While it is true that the different photoreceptors are sensitive across a range of different light intensities, they are also maximally sensitive to different colours or wavelengths of light, and as a result, each class of photoreceptor has a different peak sensitivity. Rod photoreceptors have their peak sensitivity at 498 nm light (which would appear to us as green), melanopsin is maximally sensitive to 480 nm (blue) light, and most mammals express two distinct classes of cone photoreceptors, which in the majority of rodents are maximally sensitive to approximately 360 nm (UV) and approximately508 nm (green) light respectively. As a consequence, the different photoreceptive systems not only show differences in their absolute sensitivities, but in addition, they are differentially stimulated by different wavelengths of light. Theoretically, this characteristic difference in the spectral sensitivity of the photoreceptors could add to the detection of light intensities over the day-night cycle and thereby to the capacity of the SCN to adjust to it. Such a possibility was first suggested by Foster and colleagues [10] and shown for fish by Pauers and colleagues [11].Walmsley et al. make use of a sophisticated experimental design to show the functional role of colour for the circadian system. Environmental light measurements were performed in Manchester, which lies 53 degrees north of the equator, as a function of solar angle relative to the horizon. Measurements were performed between August and October of 2005. The spectral measurements showed a reduction of irradiance and an increasing amount of short-wavelength light during twilight when the sun is below the horizon (Fig 1). This is a consequence of the differential scattering of shorter wavelengths of light by particles in the atmosphere and filtering of long wavelength light by the Chappuis band of the ozone layer. Based on the known spectral sensitivities of the short- and medium-wavelength—sensitive cone opsins, the excitation of the two pigments at different solar angles was calculated. Relative to the medium-wavelength—sensitive cone opsin, excitation of the short-wavelength—sensitive cone opsin decreases with increasing elevation of the sun above the horizon. The spectral composition of light reaching the earth shows less day-to-day variability in spectral composition than in irradiance, and thus, it may have a high predictive value about the position of the sun, as originally predicted by Foster (e.g., 2001).Open in a separate windowFig 1Colour detection by the circadian system.Colour detection by the circadian system. (A) Spectral changes in light reaching the earth during twilight. At negative solar angles, short wavelength light is dominant, while at positive solar angles, long wavelength light is dominant. (B) Schematic overview of light signalling to the SCN resulting in entrainment to a light-dark cycle. Light is the main entraining signal that adjusts the endogenous period length to the day-night cycle. Electrical activity of SCN neurons is the main output signal of the SCN, which leads to temporal regulation of behavioural activity. (C) Schematic depiction of two types of light-responsive neurons observed in the SCN as shown by Walmsley and colleagues: the colour-sensitive neuron (upper traces) and the brightness-sensitive neurons (lower traces). Image credit: Hester van Diepen.The information about changes in spectral composition of light over the day were used to simulate twilight in laboratory conditions to study whether mice make use of these changes in colour as an estimation of the time of the day. Electrophysiological recordings from SCN neurons revealed that a subpopulation of light-responsive neurons is sensitive to changes in the spectral composition of daylight. These neurons were detected based on the presence of a response to changes in spectral composition of the light source, consisting of three light-emitting diodes (LEDs) with narrow band emittance at 365 nm, 460 nm, and 600 nm. These wavelengths maximally stimulate the short-wavelength, UV sensitive cone, melanopsin, and a red knock-in cone that substitutes the normal green cone and enhances discrimination between photoreceptors.In addition to being sensitive to spectral composition changes, some neurons showed colour-opponency in response to selective activation of short-wavelength—sensitive opsins versus long-wavelength—sensitive opsins or vice versa (Fig 1). Cone photoreceptors display colour-opponency, most likely by combining signals from separate classes of cone photoreceptors in an opposing way [12,13]. The SCN may make use of this antagonistic effect by determination of the relative activation of the cone photoreceptors to various wavelengths of light. Since the two classes of photoreceptors in the mammalian retina are specifically sensitive to short-wavelength and long-wavelength light, the blue-yellow colour discrimination is a reliable way in which the SCN can detect transitions from twilight to daylight. In fact, behavioural experiments in mice showed that changes in colour are required for appropriate biological timing with respect to the solar cycle.It is of utmost importance that the SCN is appropriately aligned with the environmental light-dark cycle. In rodents, the SCN consists of about 20,000 cell autonomous oscillators that are capable of producing circadian rhythms with a period deviating slightly from 24 hours. For proper function, the cells have to be mutually synchronized, and as an ensemble they should synchronize to the environmental cycle. Direct retinal input to the SCN, via the retinohypothaloamic tract (RHT), originates exclusively from pRGCs [14]. The pRGCs can be activated by rod and cone photoreceptors via synaptic connections to the outer retina [15]. Upon activation by light, photoreceptors undergo a transformational change from the inactive state to the active state, which results in a signalling cascade that ultimately leads to the generation of action potentials in the retinal ganglion cells and in the optic tract. The initial response of the classical photoreceptors is a hyperpolarization, while the conformational change of melanopsin leads to a depolarization. The present view, emerging from the various studies, is that light information reaches the SCN via all retinal photoreceptive systems. The ability of SCN neurons to not only determine the amount of light but also the wavelength of light by comparison of the relative activation of the different photoreceptors provides the SCN with additional information. The detection of changes in spectral composition may be an additive way to detect the time of the day-night cycle, as compared to irradiance detection alone. The amount of light perceived by the SCN can vary over the day, caused by covering of the sun with clouds or hiding of a mammal in its burrow [16]. The spectral composition of light during the lower light intensity time point will not change. Therefore, this perception system provides a refinement in the ability of the SCN to estimate time of day, which would not have been possible by the estimation of irradiance per se. As at least 90% of mammalian species can discriminate colour on the basis of at least two classes of cone opsins [17], it would be interesting to investigate to what degree other mammals also make use of colour to tell time of day. 相似文献
9.
Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina 总被引:2,自引:0,他引:2
Zaidi FH Hull JT Peirson SN Wulff K Aeschbach D Gooley JJ Brainard GC Gregory-Evans K Rizzo JF Czeisler CA Foster RG Moseley MJ Lockley SW 《Current biology : CB》2007,17(24):2122-2128
As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (lambda(max)) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus ( approximately 480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all "visual" responses to light. 相似文献
10.
Circadian photoentrainment is the process by which the brain's internal clock becomes synchronized with the daily external cycle of light and dark. In mammals, this process is mediated exclusively by a novel class of retinal ganglion cells that send axonal projections to the suprachiasmatic nuclei (SCN), the region of the brain that houses the circadian pacemaker. In contrast to their counterparts that mediate image-forming vision, SCN-projecting RGCs are intrinsically sensitive to light, independent of synaptic input from rod and cone photoreceptors. The recent discovery of these photosensitive RGCs has challenged the long-standing dogma of retinal physiology that rod and cone photoreceptors are the only retinal cells that respond directly to light and has explained the perplexing finding that mice lacking rod and cone photoreceptors can still reliably entrain their circadian rhythms to light. These SCN-projecting RGCs selectively express melanopsin, a novel opsin-like protein that has been proposed as a likely candidate for the photopigment in these cells. Research in the past three years has revealed that disruption of the melanopsin gene impairs circadian photo- entrainment, as well as other nonvisual responses to light such as the pupillary light reflex. Until recently, however, there was no direct demonstration that melanopsin formed a functional photopigment capable of catalyzing G-protein activation in a light-dependent manner. Our laboratory has recently succeeded in expressing melanopsin in a heterologous tissue culture system and reconstituting a pigment with the 11-cis-retinal chromophore. In a reconstituted biochemical system, the reconstituted melanopsin was capable of activating transducin, the G-protein of rod photoreceptors, in a light-dependent manner. The absorbance spectrum of this heterologously expressed melanopsin, however, does not match that predicted by previous behavioral and electophysiological studies. Although melanopsin is clearly the leading candidate for the elusive photopigment of the circadian system, further research is needed to resolve the mystery posed by its absorbance spectrum and to fully elucidate its role in circadian photoentrainment. 相似文献
11.
Enezi J Revell V Brown T Wynne J Schlangen L Lucas R 《Journal of biological rhythms》2011,26(4):314-323
Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photosensitive retinal ganglion cells expressing the photopigment melanopsin. These mRGCs are especially important contributors to circadian entrainment, the pupil light reflex, and other so-called nonimage-forming (NIF) responses. The spectral sensitivity of melanopsin phototransduction has been addressed in several species by comparing responses to a range of monochromatic stimuli. The resultant action spectra match the predicted profile of an opsin:vitamin A-based photopigment (nomogram) with a peak sensitivity (λ(max)) around 480 nm. It would be most useful to be able to use this spectral sensitivity function to predict melanopsin's sensitivity to broad-spectrum, including "white," lights. However, evidence that melanopsin is a bistable pigment with an intrinsic light-dependent bleach recovery mechanism raises the possibility of a more complex relationship between spectral quality and photoreceptor response. Here, we set out to empirically determine whether simply weighting optical power at each wavelength according to the 480-nm nomogram and integrating across the spectrum could predict melanopsin sensitivity to a variety of polychromatic stimuli. We show that pupillomotor and circadian responses of mice relying solely on melanopsin for their photosensitivity (rd/rd cl) can indeed be accurately predicted using this methodology. Our data therefore suggest that the 480-nm nomogram may be employed as the basis for a new photometric measure of light intensity (which we term "melanopic") relevant for melanopsin photoreception. They further show that measuring light in these terms predicts the melanopsin response to light of divergent spectral composition much more reliably than other methods for quantifying irradiance or illuminance currently in widespread use. 相似文献
12.
Jan Fahrenkrug Birgitte Falktoft Birgitte Georg Jens Hannibal Sarah B. Kristiansen Thomas K. Klausen 《The Journal of biological chemistry》2014,289(51):35482-35493
The G protein-coupled light-sensitive receptor melanopsin is involved in non-image-forming light responses including circadian timing. The predicted secondary structure of melanopsin indicates a long cytoplasmic tail with many potential phosphorylation sites. Using bioinformatics, we identified a number of amino acids with a high probability of being phosphorylated. We generated antibodies against melanopsin phosphorylated at Ser-381 and Ser-398, respectively. The antibody specificity was verified by immunoblotting and immunohistochemical staining of HEK-293 cells expressing rat melanopsin mutated in Ser-381 or Ser-398. Using the antibody recognizing phospho-Ser-381 melanopsin, we demonstrated by immunoblotting and immunohistochemical staining in HEK-293 cells expressing rat melanopsin that the receptor is phosphorylated in this position during the dark and dephosphorylated when light is turned on. On the contrary, we found that melanopsin at Ser-398 was unphosphorylated in the dark and became phosphorylated after light stimulation. The light-induced changes in phosphorylation at both Ser-381 and Ser-398 were rapid and lasted throughout the 4-h experimental period. Furthermore, phosphorylation at Ser-381 and Ser-398 was independent of each other. The changes in phosphorylation were confirmed in vivo by immunohistochemical staining of rat retinas during light and dark. We further demonstrated that mutation of Ser-381 and Ser-398 in melanopsin-expressing HEK-293 cells affected the light-induced Ca2+ response, which was significantly reduced as compared with wild type. Examining the light-evoked Ca2+ response in a melanopsin Ser-381 plus Ser-398 double mutant provided evidence that the phosphorylation events were independent. 相似文献
13.
Leonardo H. R. G. Lima Ana C. Scarparo Mauro C. Isoldi Maria A. Visconti Ana M. L. Castrucci 《Biological Rhythm Research》2006,37(5):393-404
The vertebrate pigment cell, with the exception of mammals and birds, is able to provide the animal with rapid colour changes, which involve dispersion and aggregation of pigment granules in response to hormonal and neuronal agents, and in some cases as a direct response to light. The search for the mechanisms through which Xenopus leavis melanophores respond to light led to the discovery of a new photopigment, melanopsin, with a different spectral sensitivity to that of rhodopsin. This photopigment was also found in mammalian retinal ganglion cells that project to the suprachiasmatic nucleus and other non-visual retinorecipient areas. Herein we demonstrate (by RT-PCR, cloning and sequencing) for the first time that chick melanocytes express melanopsin, and confirmed the presence of the protein by immunocytochemistry. In the chicken retina, we revealed by immunocytochemistry that ganglion cells express melanopsin, but the highest density of immunopositive cells was found in the inner nuclear layer. Quantitative PCR showed that the retina of animals kept in 6 h light: 18 h dark possessed three-fold higher melanopsin mRNA content than animals kept in longer photoperiod, thus demonstrating that light modulates melanopsin expression in chickens. 相似文献
14.
The relative contribution of rods, cones, and melanopsin to non-image-forming (NIF) responses under light conditions differing in irradiance, duration, and spectral composition remains to be determined in humans. NIF responses to a polychromatic light source may be very different to that predicted from the published human action spectra data, which have utilized narrow band monochromatic light and demonstrated short wavelength sensitivity. To test the hypothesis that only melanopsin is driving NIF responses in humans, monochromatic blue light (lambda(max) 479 nm) was matched with polychromatic white light for total melanopsin-stimulating photons at three light intensities. The ability of these light conditions to suppress nocturnal melatonin production was assessed. A within-subject crossover design was used to investigate the suppressive effect of nocturnal light on melatonin production in a group of diurnally active young male subjects aged 18-35 yrs (24.9+/-3.8 yrs; mean+/-SD; n=11). A 30 min light pulse, individually timed to occur on the rising phase of the melatonin rhythm, was administered between 23:30 and 01:30 h. Regularly timed blood samples were taken for measurement of plasma melatonin. Repeated measures two-way ANOVA, with irradiance and light condition as factors, was used for statistical analysis (n=9 analyzed). There was a significant effect of both light intensity (p<0.001) and light condition (p<0.01). Polychromatic light was more effective at suppressing nocturnal melatonin than monochromatic blue light matched for melanopsin stimulation, implying that the melatonin suppression response is not solely driven by melanopsin. The findings suggest a stimulatory effect of the additional wavelengths of light present in the polychromatic light, which could be mediated via the stimulation of cone photopigments and/or melanopsin regeneration. The results of this study may be relevant to designing the spectral composition of polychromatic lights for use in the home and workplace, as well as in the treatment of circadian rhythm disorders. 相似文献
15.
目的 研究昼夜节律的改变对视网膜感光视蛋白melanopsin表达的影响.方法 出生14 d (P14)C57BL/6J小鼠随机分为实验组和正常对照组,实验组每天给予24 h持续光照,对照组模拟正常昼夜节律每天给予12 h光照、12 h黑暗环境,运用免疫荧光染色结合RT-PCR技术,分别检测实验组和对照组小鼠在光照1周后和8周后视网膜感光视蛋白melanopsin的表达情况.结果 免疫荧光染色结果显示感光视蛋白melanopsin主要位于视网膜神经节细胞层,少部分位于内核层.小鼠光照1周后melanopsin阳性细胞的表达数目实验组少于对照组;RT-PCR结果示小鼠光照1周和8周时melanopsin的mRNA含量实验组均少于各自的对照组,两者具有统计学意义(P<0.01).结论 持续光照可以减少视网膜感光视蛋白melanopsin的表达,提示melanopsin阳性神经节细胞为光敏感性细胞,其表达可能对维持正常的昼夜节律有重要作用. 相似文献
16.
Melanopsin forms a functional short-wavelength photopigment 总被引:5,自引:0,他引:5
Recently, melanopsin has emerged as the leading candidate for the elusive photopigment of the mammalian circadian system. This novel opsin-like protein is expressed in retinal ganglion cells that form the retinohypothalamic tract, a neuronal connection between the retina and the suprachiasmatic nucleus. These hypothalamic structures contain the circadian pacemaker, which generates daily rhythms in physiology and behavior. In mammals, proper synchronization of these rhythms to the environmental light-dark cycle requires retinal input. Surprisingly, rod and cone photoreceptors are not required. Instead, the melanopsin-containing ganglion cells are intrinsically sensitive to light, perhaps responding via a melanopsin-based signaling pathway. To test this hypothesis, we have characterized melanopsin following heterologous expression in COS cells. We found that melanopsin absorbed maximally at 424 nm after reconstitution with 11-cis-retinal. Furthermore, melanopsin activated the photoreceptor G-protein, transducin, in a light-dependent manner. In agreement with the measured absorbance spectrum, melanopsin was most efficiently excited by blue light (420-440 nm). In contrast, published action spectra suggest that the photopigment underlying the intrinsic light sensitivity of SCN-projecting RGCs has an absorption maximum near 484 nm. In summary, our experiments constitute the first direct demonstration that melanopsin forms a photopigment capable of activating a G-protein, but its spectral properties are not consistent with the action spectrum for circadian entrainment. 相似文献
17.
Brown TM Gias C Hatori M Keding SR Semo M Coffey PJ Gigg J Piggins HD Panda S Lucas RJ 《PLoS biology》2010,8(12):e1000558
Photoreception in the mammalian retina is not restricted to rods and cones but extends to a subset of retinal ganglion cells expressing the photopigment melanopsin (mRGCs). These mRGCs are known to drive such reflex light responses as circadian photoentrainment and pupillomotor movements. By contrast, until now there has been no direct assessment of their contribution to conventional visual pathways. Here, we address this deficit. Using new reporter lines, we show that mRGC projections are much more extensive than previously thought and extend across the dorsal lateral geniculate nucleus (dLGN), origin of thalamo-cortical projection neurons. We continue to show that this input supports extensive physiological light responses in the dLGN and visual cortex in mice lacking rods+cones (a model of advanced retinal degeneration). Moreover, using chromatic stimuli to isolate melanopsin-derived responses in mice with an intact visual system, we reveal strong melanopsin input to the ~40% of neurons in the LGN that show sustained activation to a light step. We demonstrate that this melanopsin input supports irradiance-dependent increases in the firing rate of these neurons. The implication that melanopsin is required to accurately encode stimulus irradiance is confirmed using melanopsin knockout mice. Our data establish melanopsin-based photoreception as a significant source of sensory input to the thalamo-cortical visual system, providing unique irradiance information and allowing visual responses to be retained even in the absence of rods+cones. These findings identify mRGCs as a potential origin for aspects of visual perception and indicate that they may support vision in people suffering retinal degeneration. 相似文献
18.
Holthues H Engel L Spessert R Vollrath L 《Biochemical and biophysical research communications》2005,326(1):160-165
The directly light-sensitive chick pineal gland contains at least two photopigments. Pinopsin seems to mediate the acute inhibitory effect of light on melatonin synthesis, whereas melanopsin may act by phase-shifting the intrapineal circadian clock. In the present study we have investigated, by means of quantitative RT-PCR, the daily rhythm of photopigment gene expression as monitored by mRNA levels. Under a 12-h light/12-h dark cycle, the mRNA levels of both pigments were 5-fold higher in the transitional phase from light to dark than at night, both in vivo and in vitro. Under constant darkness in vivo and in vitro, the peak of pinopsin mRNA levels was attenuated, whereas that of melanopsin was not. Thus, whereas the daily rhythm of pinopsin gene expression is dually regulated by light plus the intrapineal circadian oscillator, that of melanopsin appears to depend solely on the oscillator. 相似文献
19.
Melanopsin is the photoreceptor molecule of intrinsically photosensitive retinal ganglion cells, which serve as the input for various nonvisual behavior and physiological functions fundamental to organisms. The retina, therefore, possess a melanopsin-based nonvisual system in addition to the visual system based on the classical visual photoreceptor molecules. To elucidate the molecular properties of melanopsin, we have exogenously expressed mouse melanopsin in cultured cells. We were able to obtain large amounts of purified mouse melanopsin and conducted a comprehensive spectroscopic study of its photochemical properties. Melanopsin has an absorption maximum at 467 nm, and it converts to a meta intermediate having an absorption maximum at 476 nm. The melanopsin photoreaction is similar to that of squid rhodopsin, exhibiting bistability that results in a photosteady mixture of a resting state (melanopsin containing 11-cis-retinal) and an excited state (metamelanopsin containing all-trans-retinal) upon sustained irradiation. The absorption coefficient of melanopsin is 33000 ± 1000 M(-1) cm(-1), and its quantum yield of isomerization is 0.52; these values are also typical of invertebrate bistable pigments. Thus, the nonvisual system in the retina relies on a type of photoreceptor molecule different from that of the visual system. Additionally, we found a new state of melanopsin, containing 7-cis-retinal (extramelanopsin), which forms readily upon long-wavelength irradiation (yellow to red light) and photoconverts to metamelanopsin with short-wavelength (blue light) irradiation. Although it is unclear whether extramelanopsin would have any physiological role, it could potentially allow wavelength-dependent regulation of melanopsin functions. 相似文献
20.
Semo M Gias C Ahmado A Sugano E Allen AE Lawrence JM Tomita H Coffey PJ Vugler AA 《PloS one》2010,5(11):e15009
Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA) is a well-documented but poorly understood phenomenon during which animals attribute salience to light and remove themselves from it. Here, using genetically modified mice and an open field behavioural paradigm, we investigate the role of melanopsin in BLA. While wildtype (WT), melanopsin knockout (Opn4(-/-)) and rd/rd cl (melanopsin only (MO)) mice all exhibit BLA, our novel methodology reveals that isolated melanopsin photoreception produces a slow, potentiating response to light. In order to control for the involvement of pupillary constriction in BLA we eliminated this variable with topical atropine application. This manipulation enhanced BLA in WT and MO mice, but most remarkably, revealed light aversion in triple knockout (TKO) mice, lacking three elements deemed essential for conventional photoreception (Opn4(-/-) Gnat1(-/-) Cnga3(-/-)). Using a number of complementary strategies, we determined this response to be generated at the level of the retina. Our findings have significant implications for the understanding of how melanopsin signalling may modulate aversive responses to light in mice and humans. In addition, we also reveal a clear potential for light perception in TKO mice. 相似文献