Intrinsically photosensitive retinal ganglion cells

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light in the absence of all rod and cone photoreceptor input. The existence of these ganglion cell photoreceptors, although predicted from observations scattered over many decades, was not established until it was shown that a novel photopigment, melanopsin, was expressed in retinal ganglion cells of rodents and primates. Phototransduction in mammalian ipRGCs more closely resembles that of invertebrate than vertebrate photoreceptors and appears to be mediated by transient receptor potential channels. In the retina, ipRGCs provide excitatory drive to dopaminergic amacrine cells and ipRGCs are coupled to GABAergic amacrine cells via gap junctions. Several subtypes of ipRGC have been identified in rodents based on their morphology, physiology and expression of molecular markers. ipRGCs convey irradiance information centrally via the optic nerve to influence several functions including photoentrainment of the biological clock located in the hypothalamus, the pupillary light reflex, sleep and perhaps some aspects of vision. In addition, ipRGCs may also contribute irradiance signals that interface directly with the autonomic nervous system to regulate rhythmic gene activity in major organs of the body. Here we review the early work that provided the motivation for searching for a new mammalian photoreceptor, the ground-breaking discoveries, current progress that continues to reveal the unusual properties of these neuron photoreceptors, and directions for future investigation.Keywords: Melanopsin, Circadian rhythms, Suprachiasmatic nucleus, Retina digitalcommons.unl.edu P i c k a r d & S o l l a r S i n R e v P h y s i o l B i o c h e m P h a R m a c o l1 6 2 ( 2 0 1 2 ) Early Hints of a Third Photoreceptor in the Mammalian RetinaThe perception of shapes, color and objects moving in the world begins in the outer retina where light is absorbed by photopigments that are integral membrane apoproteins (opsins) covalently linked to a retinaldehyde chromophore in the rod and cone photoreceptors. The capturing of photons by rod and cone photoreceptors initiates a signaling cascade in which photon capture is converted into an electrical signal. The simplest common pathway these signals take from the eye to the brain is from the photoreceptors to bipolar cells to ganglion cells. Retinal ganglion cells (RGCs) convey the signals centrally as action potentials, transmitted via their axons in the optic nerve, to higher brain regions for integration and the further processing required for conscious visual perception (Fig. 1). Among non-mammalian vertebrates, photoreceptors are also found in locations outside the retina, including the pineal gland and in the brain itself. These extra-ocular photoreceptors mediate tasks not associated directly with visual perception (non-image forming functions such as hormone regulation). However, since the pioneering descriptions of the vertebrate retina by Santiago Ramón y Cajal in the late 1800s, it was believed that t...

Melanopsin expressing human retinal ganglion cells: Subtypes, distribution, and intraretinal connectivity

“…However, not all close appositions between DA processes and melanopsin dendrites may represent synapses. In mice, electron microscopy of the OFF layer revealed that not all close apposition between melanopsin processes and tyrosine hydroxylase containing elements represents genuine synapses (Pickard & Sollars, 2010). The appositions between melanopsin-ir RGCs and DAC occurred not only via melanopsin-ir dendrites, but also by recently identified intraretinal axon collaterals (Prigge et al, 2016).…”

“…We found, as reported previously in rodents and in monkeys (Liao et al, 2016;Ostergaard et al, 2007;Vugler et al, 2007), that the M1 subtype with stratifications in the outermost (OFF) layer of IPL displayed many close appositions most likely representing synaptic appositions with dopaminergic (tyrosine hydroxylase) amacrine cells (DAC) in the peripheral and central retina. In mice, electron microscopy of the OFF layer revealed that not all close apposition between melanopsin processes and tyrosine hydroxylase containing elements represents genuine synapses (Pickard & Sollars, 2010). In mice, electron microscopy of the OFF layer revealed that not all close apposition between melanopsin processes and tyrosine hydroxylase containing elements represents genuine synapses (Pickard & Sollars, 2010).…”

Diverse types of ganglion cell photoreceptors in the mammalian retina

“…Moreover, two additional subpopulations of ipRGCs (M4 and M5) with particularly low levels of melanopsin expression and dendrites in the ON sublamina of the IPL have recently been uncovered using novel melanopsin reporter mouse lines (Ecker et al, 2010). Many excellent recent reviews have emphasized the mechanisms of phototransduction in ipRGCs and role of these cells in physiology and disease (Bailes and Lucas, 2010; Do and Yau, 2010; Guler et al, 2007; Hankins et al, 2008; Hatori and Panda, 2010; Pickard and Sollars, 2010, 2011; Schmidt et al, 2011). Our review emphasizes the identification of ipRGC subtypes in the mammalian retina and highlights the current knowledge of the morphological and functional diversity of these novel photoreceptors.…”

Functional organization of autonomic neural pathways

“…Uniquely among autonomic motor pathways, accommodation can be controlled easily at will: we can choose where in the visual plane we wish to focus as easily as we can choose any other motor activity. Pupilloconstriction, which is largely under subconscious reflex control, 8 , 10 is mediated via an oculomotor parasympathetic pathway from the olivary pretectal nucleus that receives input from a recently described population of light-sensitive retinal ganglion cells 11 , 12 …”

“…Accommodation (focus) and reduction of pupil diameter are both under precise parasympathetic control, using retinal inputs 12 . Elsewhere, auditory input can modulate sympathetic pathways controlling the cutaneous circulation and the heart, whereby a sudden loud noise leads to transient blanching of the skin and increased heart rate 2 , 44 .…”