Melanopsin phototransduction: Slowly emerging from the dark

Nuffield Department of Clinical Neuroscience, Nuffield Laboratory of Ophthalmology, John Radcliffe Hospital, Headley Way, Oxford, United Kingdom.
Progress in brain research (Impact Factor: 2.83). 08/2012; 199:19-40. DOI: 10.1016/B978-0-444-59427-3.00002-2
Source: PubMed


Melanopsin expressing retinal ganglion cells represent a third class of ocular photoreceptors and are involved in irradiance detection and non-image-forming responses to light including pupil constriction, circadian entrainment, and regulation of sleep. Over recent years, there has been a rapid increase in our understanding of the anatomical variety of pRGC subtypes, the regions of the brain which they innervate, and the behavioral responses of melanopsin-based light detection. However, by contrast, our understanding of the intracellular signaling cascade initiated following activation of melanopsin has, until recently, remained poorly characterized. This chapter focus on the melanopsin signaling pathway, detailing the cellular mechanisms of phototransduction that occur within pRGCs, highlighting recent advances, but also the gaps in our understanding of this important light detecting system.

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    • "Outer retinal photoreceptors (rods and cones) are required for such IF processes as identifying prey and thus efferent innervation is essential if the lateral line is to be affected by such stimuli. However, the physiological properties of rods and cones make them less suited for monitoring overall light levels and this is thought to be the primary reason the mammalian retina contains a population melanopsin-containing pRGCs, whose sluggish but long lasting responses make them ideal for detecting overall irradiance (Bailes & Lucas, 2010; Hughes et al., 2012). It is therefore conceivable that melanopsin within the lateral line serves a similar role and modulates lateral line activity in response to longer term changes in ambient light levels. "
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    ABSTRACT: Using immunohistochemistry and Western blot analysis we demonstrate that melanospin is localised in cells around the central pore of lateral line neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a known photoreceptor pigment with diverse functions in vertebrates, we suggest that the lateral line of Xenopus laevis, which is primarily a mechanorecptor, may also be light sensitive. Potential functions of such photosensitivity are discussed, including its role in mediating locomotor responses following dermal illumination. © 2015. Published by The Company of Biologists Ltd.
    Journal of Experimental Biology 07/2015; DOI:10.1242/jeb.125203 · 2.90 Impact Factor
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    • "As previously stated, melanopsin shares both sequence identity and some similarities in signaling with invertebrate pigments compared to the other vertebrate opsin classes; for example, the involvement of a Gq/11-type G protein and the phosphoinositide pathway. After the photostimulation of melanopsin, PLC is activated, and the ultimate event in the mammalian retinal ganglion cells is the influx of calcium through TRP channels, and action potentials [66]. Interestingly, inositol trisphosphate (IP3) is not necessary for the calcium rise. "
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    ABSTRACT: Melanopsin has been implicated in the mammalian photoentrainment by blue light. This photopigment, which maximally absorbs light at wavelengths between 470 and 480 nm depending on the species, is found in the retina of all classes of vertebrates so far studied. In mammals, melanopsin activation triggers a signaling pathway which resets the circadian clock in the suprachiasmatic nucleus (SCN). Unlike mammals, Drosophila melanogaster and Danio rerio do not rely only on their eyes to perceive light, in fact their whole body may be capable of detecting light and entraining their circadian clock. Melanopsin, teleost multiple tissue (tmt) opsin and others such as neuropsin and va-opsin, are found in the peripheral tissues of Danio rerio, however, there are limited data concerning the photopigment/s or the signaling pathway/s directly involved in light detection. Here, we demonstrate that melanopsin is a strong candidate to mediate synchronization of zebrafish cells. The deduced amino acid sequence of melanopsin, although being a vertebrate opsin, is more similar to invertebrate than vertebrate photopigments, and melanopsin photostimulation triggers the phosphoinositide pathway through activation of a Gq/11-type G protein. We stimulated cultured ZEM-2S cells with blue light at wavelengths consistent with melanopsin maximal absorption, and evaluated the time course expression of per1b, cry1b, per2 and cry1a. Using quantitative PCR, we showed that blue light is capable of slightly modulating per1b and cry1b genes, and drastically increasing per2 and cry1a expression. Pharmacological assays indicated that per2 and cry1a responses to blue light are evoked through the activation of the phosphoinositide pathway, which crosstalks with nitric oxide (NO) and mitogen activated protein MAP kinase (MAPK) to activate the clock genes. Our results suggest that melanopsin may be important in mediating the photoresponse in Danio rerio ZEM-2S cells, and provide new insights about the modulation of clock genes in peripheral clocks.
    PLoS ONE 09/2014; 9(9):e106252. DOI:10.1371/journal.pone.0106252 · 3.23 Impact Factor
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    • "Nonetheless, there has yet to be direct evidence showing how and when in the melanopsin-signalling pathway PKC may mediate the observed characteristics of these photoresponses. Interestingly, functional genomics have indicated the involvement of a unique isotype of PKC (PKCz) in the melanopsin cascade, one that does not require Ca 2+ and DAG for activation (Hughes et al. 2012a ; Peirson et al. 2007 ). It was reported that knockout mice lacking the PKCz gene shared strikingly similar phenotypes to those in mice where melanopsin was genetically ablated, with a reduced pupillary light refl ex, an attenuated phase-shift circadian rhythm in response to light, decreased period-lengthening under the constant dim-light conditions, and a defi ciency in SCN expression of light-induced clock genes (Peirson et al. 2007 ). "
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    ABSTRACT: In addition to classical image-forming vision, the vertebrates exhibit a range of non-image-forming light detection systems that utilise opsin photopigments. Within the CNS these systems are present in a range of anatomical locations that include both eye and brain. In mammals the eye is both responsible and required for all commonly measured responses to light. By contrast, non-mammalian vertebrates possess a wide range of intrinsically photoreceptive sites. Members of the non-visual opsin family include exorhodopsin, pinopsin, vertebrate ancient opsin (VA), parietopsin, parapinopsin, teleost multiple tissue opsin (TMT), encephalopsin (OPN3), neuropsin (OPN5), peropsin, retinal G protein-coupled receptor (RGR) and melanopsin (OPN4). Opsin-based photopigments have evolved to mediate specific photoreceptive tasks in different light environments, each exhibit functional properties that are tuned to the biological task in which they are involved. Examination of the classes of opsin involved reveals a range of adaptions particularly in spectral sensitivity, chromophore handling and signalling mechanisms. The loss of extraocular light detection in the mammals is associated with an evolutionary reduction in the non-visual opsin representation in the mammalian genome. One clear exception to this is the retention of the melanopsin (OPN4M) gene and the expression of this opsin protein in a single class of mammalian retinal ganglion cell. Exploring the diversity of melanopsin proteins in the lower vertebrates suggests that the property of chromophore biochemistry and bistability does not necessarily define an opsin class and may have evolved more than once.
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