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...

Spectral and duration sensitivity to light-at-night in ‘blind’ and sighted rodent species

“…In mammals, two arrays of retinal photoreceptors are recognized: (1) image-forming photoreceptors (IFPRs) located in the outer retina and (2) non-image-forming photoreceptors (NIFPRs) distributed in the inner retina. The melanopsin-containing NIFPRs form a few distinctive and intrinsically photosensitive retinal ganglion cells (mRGCs), which play an important role in circadian entrainment, and little if any role in visual imaging (Bailes and Lucas, 2010;Pickard and Sollars, 2010).…”

Transcranial Light Alters Melanopsin and Monoamine Production in Mouse (Mus musculus) Brain

“…In the hypothalamus, the amount of OPN4 in transcranially illuminated mice was higher than in the controls, and the amount of OPN4 was higher regardless of the duration of illumination. The commonly acknowledged and best-known route for lightmediated effects is through the eye, where OPN4-containing ipRGCs gather light information and deliver it to the SCN via RHT [6,47,48]. Besides the retina, OPN4 is also found in the vertebrate brain [25,39] along with other opsins [10,12,13,39].…”

Endogenous spontaneous ultraweak photon emission in the formation of eye-specific retinogeniculate projections before birth

“…Here, we expand our idea and point out that Müller cells (functioning as optical fibers as shown by Franze et al, 2007), Müller cell cones (i.e. the inner half of the foveola that is created of an inverted cone-shaped zone of Müller cells; Gass, 1999), discrete retinal noise by rods (Firsov et al, 2002), as well as intrinsically photosensitive retinal ganglion cells (ipRGCs) (Pickard and Sollars, 2012) might have key functions based on the occurrence of retinal UPE (Wang et al, 2011) in the development of eye-specific retinogeniculate pathways prior to birth.…”