Phototransduction in ganglion-cell photoreceptors

Abstract

A third class of photoreceptors has recently been identified in the mammalian retina. They are a rare cell type within the class of ganglion cells, which are the output cells of the retina. These intrinsically photosensitive retinal ganglion cells support a variety of physiological responses to daylight, including synchronization of circadian rhythms, modulation of melatonin release, and regulation of pupil size. The goal of this review is to summarize what is currently known concerning the cellular and biochemical basis of phototransduction in these cells. I summarize the overwhelming evidence that melanopsin serves as the photopigment in these cells and review the emerging evidence that the downstream signaling cascade, including the light-gated channel, might resemble those found in rhabdomeric invertebrate photoreceptors.Keywords Melanopsin . ipRGC . Photoreceptor . Rhabdomeric . Retina . Ganglion cell . Suprachiasmatic nucleus . TRPC Within the past decade, the existence of a previously unknown class of photoreceptor in the mammalian retina has come to light. These directly photosensitive neurons differ radically in form and function from the well-known rod and cone photoreceptors. They are a rare variety of retinal ganglion cells (RGCs), the class of retinal neurons sending axons through the optic nerve to synapse in the brain. For at least the prior century, it had gone without question that ganglion cells were entirely dependent on polysynaptic influences from rods and cones for their responsiveness to light (indeed, even today there is no reason to doubt this for most ganglion cells). However, as the new millennium dawned, this dogma was being challenged by behavioral studies showing the persistence of certain reflex responses to light in photoreceptor degenerate animals, e.g., [14,15,35,36], and the presence of a possible photopigment, melanopsin, in a rare population of ganglion cells [18,19,21,49,50]. In short order, it became clear that these cells possessed a capacity for autonomous phototransduction [5]. These intrinsically photosensitive RGCs (ipRGCs) are now recognized as playing key roles in synchronizing circadian rhythms to the day-night cycle, mediating the pupillary response to light, and modulation of melatonin release by the pineal gland. Many aspects of this rapidly developing story have been thoroughly summarized elsewhere [4,6,14,16,31,44,54,61]. The reader is referred to these reviews for background on the intellectual origins of the discovery of melanopsin and the ipRGCs, on their structure and physiology, and on their contribution to circadian photoentrainment and other nonimage-forming visual functions. The goal of the present review is to summarize the current state of knowledge concerning the nature of the transduction process in ipRGCs. Structural and functional properties of ipRGCs relevant to the phototransduction processThe ipRGCs represent a tiny minority of the RGCs of mammalian retinas (<1-2%) [9,21,51]. Like other ganglion cells, ipRGCs extend dendritic processes...

Responses of Suprachiasmatic Nucleus Neurons to Light and Dark Adaptation: Relative Contributions of Melanopsin and Rod–Cone Inputs

“…The capacity of ipRGCs to resist bleaching by light has been proposed to derive from the invertebrate-like phototransduction mechanisms of the melanopsin photopigment (Isoldi et al, 2005;Berson, 2007;Nayak et al, 2007). This maintenance of photic responsiveness is attributed to the bistable nature of melanopsin and its ability to use light to regenerate the chromophore as suggested in several previous in vitro (Melyan et al, 2005;Panda et al, 2005) and in vivo (Mure et al, 2007) studies.…”

Phototransduction and retinal degeneration in Drosophila

“…The work on phototoxicity in Drosophila raises the question as to whether the visual impairment in mammals that results from exposure to continuous light also is due to formation of stable rhodopsin/arrestin complexes and loss of rhodopsin. Finally, the recent indications that the ipRGCs operate through a visual cascade remarkably similar to that in Drosophila [11] have resulted in renewed interest in the mechanism of Drosophila phototransduction.…”

“…Did they evolve separately? During the last few years, it has become clear that there is a small subset of retinal ganglion cells that are intrinsically photosensitive (ipRGCs), and which function in photoentrainment of circadian rhythm and in light-induced pupillary constriction [11]. Moreover, it appears that the phototransduction cascade in the ipRGCs bears striking similarities to that in fly photoreceptors.…”

Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins

“…1A). Light-induced (i.e., photochemical) isomerization of PSB11 to its all-trans isomer (PSBAT) triggers an opsin conformational change that, ultimately, activates the receptor and signaling cascade (8,9). However, similar to invertebrate and in contrast to vertebrate rhodopsins, melanopsins are bistable (10).…”