Melanopsin-Dependent Photoreception Provides Earliest Light Detection in the Mammalian Retina

Sekaran, Sumathi; Lupi, D.; Jones, Sarah L.; Sheely, Catherine; Hattar, Samer; Yau, King Wai; Lucas, Robert J.; Foster, Russell G.; Hankins, Mark W.

doi:10.1016/j.cub.2005.05.053

Cited by 175 publications

(196 citation statements)

References 49 publications

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“…Because mammalian TRPC channels are homologous to the TRP and TRP-like channels that mediate the lightactivated depolarizing responses of Drosophila photoreceptors (Minke and Parnas, 2006;Ramsey et al, 2006), these studies lend support to the hypothesis that melanopsin-related phototransduction may share a number of characteristics common to invertebrate light signaling pathways (Peirson and Foster, 2006;Berson, 2007). A hallmark of Drosophila TRP and TRP-like channels is a high permeability to Ca 2ϩ (Reuss et al, 1997), and consistent with the putative similarities between mammalian ipRGCs and Drosophila photoreceptors, it has been reported that light stimulates an increase in the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) in ipRGC somata (Sekaran et al, 2003(Sekaran et al, , 2005. However, it has yet to be determined whether ipRGC Ca 2ϩ responses result primarily from the direct flux of this cation through the light-gated channel (such as a TRPC channel).…”

Section: Introductionsupporting

confidence: 66%

“…Long-Evans rats (4 -6 per session) were killed on postnatal day 5 (P5)-P7 by halothane overexposure and decapitation. At this neonatal age, rat (Hannibal and Fahrenkrug, 2004b) and mouse (Sekaran et al, 2005) ipRGCs have been shown previously to be light responsive. After enucleation, the retinas were dissected in Hibernate-A medium (BrainBits, Springfield, IL) with 2% B27 supplements (Invitrogen, Carlsbad, CA) and 10 g/ml gentamicin.…”

Section: Methodsmentioning

confidence: 63%

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Light-Evoked Calcium Responses of Isolated Melanopsin-Expressing Retinal Ganglion Cells

Hartwick¹,

Bramley²,

Yu³

et al. 2007

J. Neurosci.

107

140

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A small number (Ͻ2%) of mammalian retinal ganglion cells express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). Light depolarizes ipRGCs and increases intracellular calcium levels ([Ca 2ϩ] i ) but the signaling cascades underlying these responses have yet to be elucidated. To facilitate physiological studies on these rare photoreceptors, highly enriched ipRGC cultures from neonatal rats were generated using anti-melanopsin-mediated plate adhesion (immunopanning). This novel approach enabled experiments on isolated ipRGCs, eliminating the potential confounding influence of rod/cone-driven input.

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Section: Introductionsupporting

confidence: 66%

Section: Methodsmentioning

confidence: 63%

Light-Evoked Calcium Responses of Isolated Melanopsin-Expressing Retinal Ganglion Cells

Hartwick¹,

Bramley²,

Yu³

et al. 2007

J. Neurosci.

107

140

View full text Add to dashboard Cite

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“…Physiologically, in mouse retina, melanopsin-expressing ipRGCs can be activated by light as early as the day of birth (9,10). Concomitantly, by postnatal day 1 (P1), ipRGCs express vesicular glutamate transporter type 2, necessary for the synaptic release of glutamate from ipRGCs (11), and project their axons to the suprachiasmatic nucleus (SCN) of the hypothalamus (12).…”

mentioning

confidence: 99%

“…Concomitantly, by postnatal day 1 (P1), ipRGCs express vesicular glutamate transporter type 2, necessary for the synaptic release of glutamate from ipRGCs (11), and project their axons to the suprachiasmatic nucleus (SCN) of the hypothalamus (12). Furthermore, the retina-SCN tract in rats can be activated by light immediately after birth (9,10,13).…”

mentioning

confidence: 99%

Melanopsin-dependent light avoidance in neonatal mice

Johnson¹,

Wu²,

Donovan³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

126

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Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) form a light-sensitive system separate from rods and cones. Direct light stimulation of ipRGCs can regulate many nonimageforming visual functions such as photoentrainment of circadian rhythms and pupil responses, and can intensify migraine headache in adults. In mice, ipRGCs are light responsive as early as the day of birth. In contrast, their eyelids do not open until 12-13 d after birth (P12-13), and light signaling from rods and cones does not begin until approximately P10. No physiological or behavioral function is established for ipRGCs in neonates before the onset of rod and cone signaling. Here we report that mouse pups as young as P6 will completely turn away from a light. Light-induced responses of ipRGCs could be readily recorded in retinas of pups younger than P9, and we found no evidence for rod-and cone-mediated visual signaling to the RGCs of these younger mice. These results confirm that negative phototaxis is evident before the onset of rod-and cone-mediated visual signaling, and well before the onset of image-forming vision. Negative phototaxis was absent in mice lacking melanopsin. We conclude that light activation of melanopsin ipRGCs is necessary and sufficient for negative phototaxis. These results strongly suggest that light activation of ipRGCs may regulate physiological functions such as sleep/wake cycles in preterm and neonatal infants.

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“…These responses depend on the opsin family member melanopsin (5), which is expressed exclusively in a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) (6)(7)(8). Mice with nonfunctional or degenerated rods and cones that also lack melanopsin show no photically influenced behavior or physiology (9,10), and intrinsic photosensitivity of retinal ganglion cells is lost in the absence of melanopsin (9,11,12). Melanopsin forms a functional photopigment when heterologously expressed in COS cells (13), Xenopus oocytes (14), Neuro-2A cells (15), or HEK-293 cells (16).…”

mentioning

confidence: 99%

Inner retinal photoreception independent of the visual retinoid cycle

Tu¹,

Owens²,

Anderson³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Mice lacking the visual cycle enzymes RPE65 or lecithin-retinol acyl transferase (Lrat) have pupillary light responses (PLR) that are less sensitive than those of mice with outer retinal degeneration (rd͞rd or rdta). Inner retinal photoresponses are mediated by melanopsinexpressing, intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting that the melanopsin-dependent photocycle utilizes RPE65 and Lrat. To test this hypothesis, we generated rpe65 ؊/؊ ; rdta and lrat ؊/؊ ; rd͞rd mutant mice. Unexpectedly, both rpe65 ؊/؊ ; rdta and lrat ؊/؊ ; rd͞rd mice demonstrate paradoxically increased PLR photosensitivity compared with mice mutant in visual cycle enzymes alone. Acute pharmacologic inhibition of the visual cycle of melanopsin-deficient mice with all-trans-retinylamine results in a near-total loss of PLR sensitivity, whereas treatment of rd͞rd mice has no effect, demonstrating that the inner retina does not require the visual cycle. Treatment of rpe65 ؊/؊ ; rdta with 9-cis-retinal partially restores PLR sensitivity. Photic sensitivity in P8 rpe65 ؊/؊ and lrat ؊/؊ ipRGCs is intact as measured by ex vivo multielectrode array recording. These results demonstrate that the melanopsin-dependent ipRGC photocycle is independent of the visual retinoid cycle.melanopsin ͉ pupillary light response ͉ retinal degeneration ͉ retinal ganglion cell ͉ visual photocycle M ice blind from outer retinal degeneration retain the ability to entrain their circadian rhythms to external light-dark cycles, have active pupillary light responses (PLRs), and exhibit photically induced melatonin suppression (1-4). These responses depend on the opsin family member melanopsin (5), which is expressed exclusively in a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) (6-8). Mice with nonfunctional or degenerated rods and cones that also lack melanopsin show no photically influenced behavior or physiology (9, 10), and intrinsic photosensitivity of retinal ganglion cells is lost in the absence of melanopsin (9,11,12). Melanopsin forms a functional photopigment when heterologously expressed in COS cells (13), Xenopus oocytes (14), Neuro-2A cells (15), or HEK-293 cells (16). Melanopsin is thus necessary for ipRGC photoreception, and is sufficient to confer photosensitivity on intrinsically insensitive cell types. Taken together, these results strongly suggest that melanopsin is the photopigment of inner retinal photoreception.All opsin photopigments use a retinoid chromophore that undergoes isomerization upon absorption of an appropriate wavelength photon. In rod photoreceptors, 11-cis-retinal chromophore is photoisomerized to all-trans-retinal which dissociates from the opsin protein (17). This all-trans-retinal photoproduct is recycled to the active (11-cis) form by enzymatic conversion in the adjacent retinal pigment epithelium (RPE) (18). The chromophore used by melanopsin in situ is not presently known. ipRGCs are physically distant from the enzymatic chromophore regeneration machinery of the RPE. It is present...

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Melanopsin-Dependent Photoreception Provides Earliest Light Detection in the Mammalian Retina

Abstract: The findings suggest that the non-image-forming pathway is functional long before the mainstream image-forming pathway during development.

Cited by 175 publications

References 49 publications

Light-Evoked Calcium Responses of Isolated Melanopsin-Expressing Retinal Ganglion Cells

Light-Evoked Calcium Responses of Isolated Melanopsin-Expressing Retinal Ganglion Cells

Melanopsin-dependent light avoidance in neonatal mice

Inner retinal photoreception independent of the visual retinoid cycle

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