Encyclopedia of Color Science and Technology

2016 Edition
| Editors: Ming Ronnier Luo

Melanopsin Retinal Ganglion Cells

  • Robert Lucas
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-8071-7_275



A subset of retinal ganglion cells characterized by their expression of melanopsin and their ability to respond directly to light. Melanopsin is an opsin protein structurally and phylogenetically related to rod and cone opsins. It binds retinaldehyde as a chromophore and activates a G-protein signaling cascade upon photon absorption. As a result, melanopsin retinal ganglion cells are depolarized by light even when physically, pharmacologically, or genetically isolated from rod and cone influences. This allows them to function as an independent origin of visual information. mRGCs are known to encode environmental brightness for such visual reflexes as circadian photoentrainment and regulating pupil size. They likely also make as yet ill-defined contributions to other visual processes including perceptual vision.

Discovery and Functions

Until around the turn of the millennium it was considered self-evident that all aspects of human vision could be ultimately attributed to the activity of rod and/or cone photoreceptors. With hindsight it is possible to find isolated examples of findings in several branches of vision science that questioned this assumption, but the concerted effort that led to the discovery of a third photoreceptor type came from researchers interested in a particular visual function – circadian entrainment [1].

Like almost all life on earth, humans have an internal circadian clock that oscillates with a period close to 24 h. In order to fulfill its function of coordinating physiology and behavior to the varying demands of the astronomical day this clock needs to be accurately set (or “entrained”) to local time. Entrainment relies upon a representation of the light:dark cycle provided by a dedicated retinal projection to the hypothalamic site of the circadian oscillator, the suprachiasmatic nuclei (or SCN). Studies of human subjects and rodent models of retinal dystrophy revealing that circadian entrainment was buffered against massive loss of rods and cones culminated in the demonstration that this function was retained even when these conventional photoreceptors were completely absent [2]. An explanation for this finding was provided by the discovery that the retinal ganglion cells projecting to the SCN are in fact directly photoreceptive [3].

Melanopsin is one of a number of opsin proteins known to be expressed outside of the eyes in nonmammalian vertebrates. It was initially discovered in the photosensitive dermal melanophores of Xenopus laevus [4]. Orthologues were subsequently identified in mammalian genomes and found to be expressed in the retinal ganglion cells innervating the SCN. These ganglion cells were shown to lack their intrinsic photosensitivity in mice lacking melanopsin [5], while inclusion of melanopsin was shown to be sufficient to induce photosensitivity in a variety of non-light-responsive cell types [6, 7, 8].

Although initially discovered in the search to understand circadian entrainment, melanopsin retinal ganglion cells are now thought to contribute to a wide variety of visual responses [9]. mRGCs project not just to the SCN but also to other parts of the hypothalamus, the pretectum, the superior colliculus, the visual thalamus, and the nucleus of the optic tract [10, 11]. Their established functions extend to providing the pupil light reflex, regulating sleep/alertness, and suppressing pineal melatonin production. There is also evidence that they regulate mood and retinal development and influence retinal physiology by controlling local circadian clocks and the activity of dopaminergic amacrine cells.

At present, the nature and extent of mRGC contributions to perceptual vision is unclear. However, the appearance of mRGC fibers in projections to the dorsal lateral geniculate nucleus and established functional connections to other cell types in the retina via gap junctions and intraretinal axonal projections raise the possibility that mRGCs could have both direct and modulatory influences on perceptual vision. In primates, at least some ipRGCs receive antagonistic input from short- and long/medium-wavelength cones and may contribute to blue:yellow discrimination [12].

Anatomy and Physiology

The defining feature of mRGCs is their expression of melanopsin and consequent intrinsic photosensitivity. In rodents, at least five morphologically distinct classes of retinal ganglion cell (termed M1 to 5) meet this criterion [13]. The best-characterized of these is the M1 class, which has the highest melanopsin expression (and the most prominent intrinsic light response) and is responsible for both circadian entrainment and the pupil light reflex. Other classes differ in their central projections, the nature and spatial extent of dendritic arborization, and their degree of melanopsin expression [13]. mRGCs described in primates thus far are more anatomically homogeneous, with all having large sparsely arborized dendritic fields located in either the inner or outer portions of the inner plexiform layer [12].

The dendrites of mRGCs are sites of melanopsin-driven phototransduction but also of synaptic inputs from bipolar and amacrine cells. As a result, in the intact retina, the spike-firing pattern of mRGCs is defined in part by melanopsin photoreception and in part by synaptic influences originating in signals from rods and cones. As mRGCs lack the membranous disks used by rods and cones to maximize photopigment concentration, they have very poor photon capture efficiency. As a result, melanopsin has an appreciable impact on mRGC firing only at rather high light intensities (several decades above the threshold for cone activation). Even at these light levels the rate of melanopsin photoisomerization is low, and its phototransduction cascade has to have high gain [14]. This is achieved by having a long activation time, with the consequence that the melanopsin light response has poor temporal resolution. Under some circumstances this phenomenon can be extreme with light-induced firing of mRGCs and melanopsin-driven pupil constriction lasting several tens of seconds after the light has been turned off. Under more natural conditions, these sensory characteristics imply that melanopsin provides a low spatiotemporal resolution signal of environmental brightness, with mRGCs relying upon input from rods and cones to encode lower light levels and to track higher frequency changes in light intensity [15].

Melanopsin, like all animal opsins, is a member of the G-protein coupled receptor superfamily of proteins. The molecular identity of the critical elements of its phototransduction cascade is unknown. However, the available evidence indicates that melanopsin couples to a G-protein of the Gq/11 class upon light exposure, which results in activation of phospholipase C and subsequent membrane depolarization by opening TRP channels [16].

Spectral Sensitivity

Measuring the spectral absorbance properties of melanopsin directly has proved challenging. It is not found in sufficient concentrations to allow direct in vivo microspectrophotometry. While it has been possible to purify melanopsin from harvested retinas and from heterologous cell-based expression systems, the quality of these preparations falls far short of that achieved with rod or cone opsins. As a result, a precise description of melanopsin’s spectral absorbance in the dark state, and following light absorption, remains elusive. Nonetheless, action spectra for melanopsin-driven activation of mRGC activation and downstream responses in a variety of mammalian species are consistent with the hypothesis that in the dark state melanopsin’s spectral sensitivity can be well described by the standard opsin:vitamin A1 template peaking around 480 nm [15]. This puts it close to the spectral sensitivity of human rod opsin but far from that of the cone photoreceptors that are conventionally considered to dominate vision at moderate and high light levels. Importantly, its spectral sensitivity is also significantly short wavelength shifted compared to V(λ) (the spectral efficiency function of photopic vision), which is used in quantifying (il)luminance. This implies that spectrally distinct natural and artificial light sources might have quite different effective intensity for melanopsin even when matched for illuminance. There is thus a need to update measurement metrics and to reconsider the spectral content of artificial sources to take account of melanopsin’s discovery [15].


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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Faculty of Life SciencesUniversity of ManchesterManchesterUK