Illumination of the Melanopsin Signaling Pathway

  title={Illumination of the Melanopsin Signaling Pathway},
  author={Satchidananda Panda and Surendra Kumar Nayak and Brice Campo and John R. Walker and John B. Hogenesch and Timothy Jegla},
  pages={600 - 604}
In mammals, a small population of intrinsically photosensitive retinal ganglion cells (ipRGCs) plays a key role in the regulation of nonvisual photic responses, such as behavioral responses to light, pineal melatonin synthesis, pupillary light reflex, and sleep latency. These ipRGCs also express melanopsin (Opn4), a putative opsin-family photopigment that has been shown to play a role in mediating these nonvisual photic responses. Melanopsin is required for the function of this inner retinal… 


Melanopsin is identified as a photopigment critically involved in the light-mediated regulation of circadian rhythms and heterologous expression of melanopsin in human embryonic kidney cells (HEK293) imparts photosensitivity upon the cell line.

Molecular Basis of Circadian Photoreception

Melanopsin is identified as a photopigment critically involved in the light-mediated regulation of circadian rhythms and heterologous expression of melanopsin in human embryonic kidney cells (HEK293) imparts photosensitivity upon the cell line.

Induction of photosensitivity by heterologous expression of melanopsin

It is concluded that mammalian melanopsin is a functional sensory photopigment, that it is the photopigsment of ganglion-cell photoreceptors, and that these photoreCEPTors may use an invertebrate-like phototransduction cascade.

Melanopsin phototransduction: beyond canonical cascades

Recent findings and discoveries are discussed that have challenged the prevailing view of melanopsin phototransduction as a single pathway that influences solely non-image forming functions.

Photochemistry of retinal chromophore in mouse melanopsin

Results indicate that even if melanopsin functions as a bistable photopigment with photo-regenerative activity native melanops in vivo must also use some other light-independent retinoid regeneration mechanism to return to the dark state, where all of the retinal is observed to be in the 11-cis form.

Melanopsin-Encoded Response Properties of Intrinsically Photosensitive Retinal Ganglion Cells

Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin.

  • Yingbin FuH. Zhong K. Yau
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
Study of mice lacking RPE65, a protein essential for the regeneration of rod and cone pigments, and exogenous all-trans-retinal was also able to rescue the low sensitivity of rpe65-/- ipRGCs suggest melanopsin could be a bistable pigment.

Immunohistochemical evidence of a melanopsin cone in human retina.

The presence of melanopsin in human cones suggests image and non-image-forming roles in visual responses at both the cone input and ganglion cell output stages and their involvement in a broad spectrum of irradiance detection functions in the visual system.

Melanopsin ganglion cells use a membrane-associated rhabdomeric phototransduction cascade.

A membrane-associated phosphoinositide cascade lies at the heart of the ipRGC phototransduction mechanism, similar to the cascade in rhabdomeric photoreceptors of invertebrate eyes, and reinforces the emerging view that these cells have a common evolutionary origin.



Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity

It is shown that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs, most likely the visual pigment of phototransducing R GCs that set the circadian clock and initiate other non–image-forming visual functions.

Melanopsin and rod–cone photoreceptive systems account for all major accessory visual functions in mice

The rod–cone and melanopsin systems together seem to provide all of the photic input for these accessory visual functions such as pupillary light reflex and circadian photo-entrainment.

Diminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice

It is reported that in mice with the melanopsin gene ablated, RGCs retrograde-labeled from the suprachiasmatic nuclei were no longer intrinsically photosensitive, although their number, morphology, and projections were unchanged.

Melanopsin Is Required for Non-Image-Forming Photic Responses in Blind Mice

It is observed that mice with both outer-retinal degeneration and a deficiency in melanopsin exhibited complete loss of photoentrainment of the circadian oscillator, pupillary light responses, photic suppression of arylalkylamine-N-acetyltransferase transcript, and acute suppression of locomotor activity by light, indicating the importance of both nonvisual and classical visual photoreceptor systems for nonvisual photic responses in mammals.

Melanopsin: An opsin in melanophores, brain, and eye.

Melanopsin mRNA is expressed in hypothalamic sites thought to contain deep brain photoreceptors and in the iris, a structure known to be directly photosensitive in amphibians, and expression in retinal and nonretinal tissues suggests a role in vision and nonvisual photoreceptive tasks.

Intrinsic light responses of retinal ganglion cells projecting to the circadian system

The intrinsic light‐activated current observed in SCN‐projecting RGCs resembles currents carried by ion channels of the transient receptor potential (trp) family, which are known to mediate the light response of invertebrate photoreceptors.

Role of Melanopsin in Circadian Responses to Light

Although melanopsin is not essential for the circadian clock to receive photic input, it contributes significantly to the magnitude of photic responses.

Characterization of an ocular photopigment capable of driving pupillary constriction in mice

This work demonstrates that transgenic mice lacking both rod and cone photoreceptors (rd/rd cl) retain a pupillary light reflex (PLR) that does not rely on local iris photoreCEPTors, and represents the first functional characterization of a non-rod, non-cone photoreceptive system in the mammalian CNS.