Isoforms of Melanopsin Mediate Different Behavioral Responses to Light

Jagannath, Aarti; Hughes, Steven; Abdelgany, A; Pothecary, Carina A.; Pretoro, Simona Di; Pires, Susana S.; Vachtsevanos, Athanasios; Pilorz, Violetta; Brown, L. M.; Hoßbach, Markus; MacLaren, Robert E.; Halford, Stephanie; Gatti, Silvia; Hankins, Mark W.; Wood, Matthew; Foster, Russell G.; Peirson, Stuart N.

doi:10.1016/j.cub.2015.07.071

Cited by 34 publications

(34 citation statements)

References 33 publications

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“…In humans, there are two isoforms of Opn4 (Jagannath et al, 2015). Thus, the low immunoreactivity of M2 cells may be due to the fact that, contrary to what occurs in other cell types, only one of the isoforms is expressed in these cells, as previously described in mice (Pires et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration in the Aging Human Retina

Esquiva

Lax

Pérez-Santonja

et al. 2017

Front. Aging Neurosci.

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In mammals, melanopsin-expressing retinal ganglion cells (mRGCs) are, among other things, involved in several non-image-forming visual functions, including light entrainment of circadian rhythms. Considering the profound impact of aging on visual function and ophthalmic diseases, here we evaluate changes in mRGCs throughout the life span in humans. In 24 post-mortem retinas from anonymous human donors aged 10–81 years, we assessed the distribution, number and morphology of mRGCs by immunostaining vertical retinal sections and whole-mount retinas with antibodies against melanopsin. Human retinas showed melanopsin immunoreactivity in the cell body, axon and dendrites of a subset of ganglion cells at all ages tested. Nearly half of the mRGCs (51%) were located within the ganglion cell layer (GCL), and stratified in the outer (M1, 12%) or inner (M2, 16%) margin of the inner plexiform layer (IPL) or in both plexuses (M3, 23%). M1 and M2 cells conformed fairly irregular mosaics, while M3 cell distribution was slightly more regular. The rest of the mRGCs were more regularly arranged in the inner nuclear layer (INL) and stratified in the outer margin of the IPL (M1d, 49%). The quantity of each cell type decrease after age 70, when the total number of mRGCs was 31% lower than in donors aged 30–50 years. Moreover, in retinas with an age greater than 50 years, mRGCs evidenced a decrease in the dendritic area that was both progressive and age-dependent, as well as fewer branch points and terminal neurite tips per cell and a smaller Sholl area. After 70 years of age, the distribution profile of the mRGCs was closer to a random pattern than was observed in younger retinas. We conclude that advanced age is associated with a loss in density and dendritic arborization of the mRGCs in human retinas, possibly accounting for the more frequent occurrence of circadian rhythm disorders in elderly persons.

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Section: Discussionmentioning

confidence: 99%

Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration in the Aging Human Retina

Esquiva

Lax

Pérez-Santonja

et al. 2017

Front. Aging Neurosci.

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“…However, the PLR and circadian entrainment are both known to be driven by M1-type pRGCs, 38 yet disruption of phase shifts and entrainment required silencing of both OPN4S and OPN4L, whereas the PLR was inhibited by silencing of only OPN4S, with no apparent additive effect of also silencing OPN4L. 79 Based on these observations it is possible that OPN4S and OPN4L are capable of driving different biochemical signals within pRGCs, influencing cellular output, and ultimately contributing to specific behavioural responses.…”

Section: Correlation Of Prgc Subtypes With Response Typesmentioning

confidence: 98%

“…79 Silencing of OPN4S alone pRGCs signalling S Hughes et al is sufficient to disrupt the PLR, whereas silencing of both OPN4S and OPN4L is necessary to attenuate the phaseshifting of locomotor activity and the induction of sleep. By contrast, negative masking was attenuated by silencing of only OPN4L, with no apparent dependence on OPN4S.…”

Section: Correlation Of Prgc Subtypes With Response Typesmentioning

confidence: 99%

Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells

Hughes

Jagannath

Rodgers

et al. 2016

Eye

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Over the past two decades there have been significant advances in our understanding of both the anatomy and function of the melanopsin system. It has become clear that rather than acting as a simple irradiance detector the melanopsin system is in fact far more complicated. The range of behavioural systems known to be influenced by melanopsin activity is increasing with time, and it is now clear that melanopsin contributes not only to multiple non-image forming systems but also has a role in visual pathways. How melanopsin is capable of driving so many different behaviours is unclear, but recent evidence suggests that the answer may lie in the diversity of melanopsin light responses and the functional specialisation of photosensitive retinal ganglion cell (pRGC) subtypes. In this review, we shall overview the current understanding of the melanopsin system, and evaluate the evidence for the hypothesis that individual pRGC subtypes not only perform specific roles, but are functionally specialised to do so. We conclude that while, currently, the available data somewhat support this hypothesis, we currently lack the necessary detail to fully understand how the functional diversity of pRGC subtypes correlates with different behavioural responses, and ultimately why such complexity is required within the melanopsin system. What we are lacking is a cohesive understanding of how light responses differ between the pRGC subtypes (based not only on anatomical classification but also based on their site of innervation); how these diverse light responses are generated, and most importantly how these responses relate to the physiological functions they underpin.

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“…However, Ca 2+ imaging demonstrated similar deactivation kinetics for murine isoforms expressed in HEK293 cells . Nevertheless, as murine melanopsin isoforms differ with the behavior response they mediate , it is possible that the variations in the phosphorylation might play a role in the regulation of melanopsin signaling driven by the presence of extracellular signals or by differences in intracellular content between different cell types/subtypes.…”

Section: Regulation Of Melanopsin Signaling Via Post‐translational Momentioning

confidence: 93%

Regulation of Melanopsin Signaling: Key Interactions of the Nonvisual Photopigment

Stachurska

Sarna

2018

Photochem & Photobiology

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Melanopsin is a G protein-coupled receptor with a peak sensitivity in the blue part of the spectrum, which plays a key role in nonvisual light-mediated signaling. Recently, its importance in forming visual pathway as well as its role in blood vessels photorelaxation was also revealed. Melanopsin was discovered in 1998 in Xenopus leavis. Since then, the melanopsin presence was demonstrated across the species. The existence of two melanopsin genes (opn4m and opn4x) as well as melanopsin isoforms resulting from alternative splicing contributes to the variety in melanopsin-regulated processes. In this review, the diversity in melanopsin-induced signaling, regulation of melanopsin activity by phosphorylation and regulation of melanopsin mRNA are discussed.

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Isoforms of Melanopsin Mediate Different Behavioral Responses to Light

Cited by 34 publications

References 33 publications

Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration in the Aging Human Retina

Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration in the Aging Human Retina

Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells

Regulation of Melanopsin Signaling: Key Interactions of the Nonvisual Photopigment

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