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Functional diversity of human intrinsically photosensitive retinal ganglion cells.

ABSTRACT: Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subset of cells that participate in image-forming and non-image-forming visual responses. Although both functional and morphological subtypes of ipRGCs have been described in rodents, parallel functional subtypes have not been identified in primate or human retinas. In this study, we used a human organ donor preparation method to measure human ipRGCs' photoresponses. We discovered three functional ipRGC subtypes with distinct sensitivities and responses to light. The response of one ipRGC subtype appeared to depend on exogenous chromophore supply, and this response is conserved in both human and mouse retinas. Rods and cones also provided input to ipRGCs; however, each subtype integrated outer retina light signals in a distinct fashion.

SUBMITTER: Mure LS

PROVIDER: S-EPMC7120228 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Functional diversity of human intrinsically photosensitive retinal ganglion cells.

Mure Ludovic S LS Vinberg Frans F Hanneken Anne A Panda Satchidananda S

Science (New York, N.Y.) 20191201 6470

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subset of cells that participate in image-forming and non-image-forming visual responses. Although both functional and morphological subtypes of ipRGCs have been described in rodents, parallel functional subtypes have not been identified in primate or human retinas. In this study, we used a human organ donor preparation method to measure human ipRGCs' photoresponses. We discovered three functional ipRGC subtypes with distinct sen ...[more]

PMID: 31806815

Similar Datasets

[Intrinsically photosensitive retinal ganglion cells].

Project description:BackgroundMelanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGC) area third class of photoreceptors in the retina in addition to rods and cones. They are a small heterogeneous population of cells primarily mediating non-image-forming visual functions.ObjectiveThis article provides an overview of the current understanding of the functions and the diversity of ipRGCs. It moreover gives an insight into clinically and translationally relevant aspects and treatment options.Material and methodsNarrative review article.ResultsipRGCs make up ~1-2% of all retinal ganglion cells and are divided into 6 specialized subtypes. With the photopigment melanopsin they can trigger light responses without rod or cone input and can relay irradiance information to various centers of the brain. Depending on the subtype, ipRGCs mediate non-image-forming tasks, such as the pupillary light reflex or synchronizing the circadian clock, and image-forming tasks, such as contrast optimization. ipRGCs exhibit differential resilience against optic nerve damage, making them an interesting study object for the development of neuroprotective strategies. In addition, melanopsin is an attractive optogenetic tool for vision restoration.ConclusionKnowledge on ipRGC physiology is indispensable for understanding frequent clinical observations. Their functional and morphological features are the subject of active research, which highlights novel translational strategies.

| S-EPMC9005408 | biostudies-literature

Functional and morphological differences among intrinsically photosensitive retinal ganglion cells.

Project description:A subset of ganglion cells in the mammalian retina express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). These cells are implicated in non-image-forming visual responses to environmental light, such as the pupillary light reflex, seasonal adaptations in physiology, photic inhibition of nocturnal melatonin release, and modulation of sleep, alertness, and activity. Morphological studies have confirmed the existence of at least three distinct subpopulations of ipRGCs, but studies of the physiology of ipRGCs at the single cell level have focused mainly on M1 cells, the dendrites of which stratify solely in sublamina a (OFF sublamina) of the retinal inner plexiform layer (IPL). Little work has been done to compare the functional properties of M1 cells to those of M2 cells, the dendrites of which stratify solely in sublamina b (ON sublamina) of the IPL. The goal of the current study was to compare the morphology, intrinsic light response, and intrinsic membrane properties of M1 and M2 cells in the mouse retina. Here we demonstrate additional morphological differences between M1 and M2 cells as well as distinct physiological characteristics of both the intrinsic light responses and intrinsic membrane properties. M2 cells displayed a more complex dendritic arborization and higher input resistance, yet showed lower light sensitivity and lower maximal light responses than M1 cells. These data indicate morphological and functional heterogeneity among ipRGCs.

| S-EPMC2752349 | biostudies-literature

Adaptation to steady light by intrinsically photosensitive retinal ganglion cells.

Project description:Intrinsically photosensitive retinal ganglion cells (ipRGCs) are recently discovered photoreceptors in the mammalian eye. These photoreceptors mediate primarily nonimage visual functions, such as pupillary light reflex and circadian photoentrainment, which are generally expected to respond to the absolute light intensity. The classical rod and cone photoreceptors, on the other hand, mediate image vision by signaling contrast, accomplished by adaptation to light. Experiments by others have indicated that the ipRGCs do, in fact, light-adapt. We found the same but, in addition, have now quantified this light adaptation for the M1 ipRGC subtype. Interestingly, in incremental-flash-on-background experiments, the ipRGC's receptor current showed a flash sensitivity that adapted in background light according to the Weber-Fechner relation, well known to describe the adaptation behavior of rods and cones. Part of this light adaptation by ipRGCs appeared to be triggered by a Ca(2+) influx, in that the flash response elicited in the absence of extracellular Ca(2+) showed a normal rising phase but a slower decay phase, resulting in longer time to peak and higher sensitivity. There is, additionally, a prominent Ca(2+)-independent component of light adaptation not typically seen in rods and cones or in invertebrate rhabdomeric photoreceptors.

| S-EPMC3645585 | biostudies-literature

Melanopsin-Encoded Response Properties of Intrinsically Photosensitive Retinal Ganglion Cells.

Project description:Melanopsin photopigment expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) plays a crucial role in the adaptation of mammals to their ambient light environment through both image-forming and non-image-forming visual responses. The ipRGCs are structurally and functionally distinct from classical rod/cone photoreceptors and have unique properties, including single-photon response, long response latency, photon integration over time, and slow deactivation. We discovered that amino acid sequence features of melanopsin protein contribute to the functional properties of the ipRGCs. Phosphorylation of a cluster of Ser/Thr residues in the C-terminal cytoplasmic region of melanopsin contributes to deactivation, which in turn determines response latency and threshold sensitivity of the ipRGCs. The poorly conserved region distal to the phosphorylation cluster inhibits phosphorylation's functional role, thereby constituting a unique delayed deactivation mechanism. Concerted action of both regions sustains responses to dim light, allows for the integration of light over time, and results in precise signal duration.

| S-EPMC4891235 | biostudies-literature

Overlapping morphological and functional properties between M4 and M5 intrinsically photosensitive retinal ganglion cells.

Project description:Multiple retinal ganglion cell (RGC) types in the mouse retina mediate pattern vision by responding to specific features of the visual scene. The M4 and M5 melanopsin-expressing, intrinsically photosensitive retinal ganglion cell (ipRGC) subtypes are two RGC types that are thought to play major roles in pattern vision. The M4 ipRGCs overlap in population with ON-alpha RGCs, while M5 ipRGCs were recently reported to exhibit opponent responses to different wavelengths of light (color opponency). Despite their seemingly distinct roles in visual processing, previous reports have suggested that these two populations may exhibit overlap in their morphological and functional properties, which calls into question whether these are in fact distinct RGC types. Here, we show that M4 and M5 ipRGCs are distinct morphological classes of ipRGCs, but they cannot be exclusively differentiated based on color opponency and dendritic morphology as previously reported. Instead, we find that M4 and M5 ipRGCs can only be distinguished based on soma size and the number of dendritic branch points in combination with SMI-32 immunoreactivity. These results have important implications for clearly defining RGC types and their roles in visual behavior.

| S-EPMC7007370 | biostudies-literature

Intrinsically photosensitive ganglion cells contribute to plasticity in retinal wave circuits.

Project description:Correlated spontaneous activity in the developing nervous system is robust to perturbations in the circuits that generate it, suggesting that mechanisms exist to ensure its maintenance. We examine this phenomenon in the developing retina, where blockade of cholinergic circuits that mediate retinal waves during the first postnatal week leads to the generation of "recovered" waves through a distinct, gap junction-mediated circuit. Unlike cholinergic waves, these recovered waves were modulated by dopaminergic and glutamatergic signaling, and required the presence of the gap junction protein connexin 36. Moreover, in contrast to cholinergic waves, recovered waves were stimulated by ambient light via activation of melanopsin-expressing intrinsically photosensitive retinal ganglion cells. The involvement of intrinsically photosensitive retinal ganglion cells in this reconfiguration of wave-generating circuits offers an avenue of retinal circuit plasticity during development that was previously unknown.

| S-EPMC3718101 | biostudies-literature

Subjective time expansion with increased stimulation of intrinsically photosensitive retinal ganglion cells.

Project description:Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain photoreceptors that are especially sensitive to blue light. Nevertheless, how blue light and ipRGCs affect time perception remains unsolved. We used the oddball paradigm and manipulated the background light to examine whether and how blue light and ipRGCs affect perceived duration. In the oddball paradigm, participants were asked to judge the duration of the target (oddball), compared to that of the standard, with a two alternative-forced-choice procedure. When the background light was controlled to be either blue or red in Experiment 1, results showed that blue light led to longer subjective duration compared to red light. Experiment 2 further clarified the contribution of the ipRGCs. A set of multi-primary projector system that could manipulate the ipRGC stimulation were used, while the color and luminance of the background lights were kept constant throughout. Results showed that increased stimulation of ipRGCs under metameric background expanded subjective time. These results suggest that ipRGC stimulation increases arousal/attention so as to expand subjective duration.

| S-EPMC6076248 | biostudies-literature

Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey.

Project description:Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are entrained to the environmental light/dark cycle via intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin and the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP). The ipRGCs regulate other nonimage-forming visual functions such as the pupillary light reflex, masking behavior, and light-induced melatonin suppression. To evaluate whether PACAP-immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we characterized the occurrence of PACAP in melanopsin-expressing ipRGCs and in the retinal target areas in the brain visualized by the anterograde tracer cholera toxin subunit B (CtB) in combination with PACAP staining. In the retina, PACAP and melanopsin were found to be costored in 99% of melanopsin-expressing cells characterized as inner and outer stratifying melanopsin RGCs. Two macaque monkeys were anesthetized and received a unilateral intravitreal injection of CtB. Bilateral retinal projections containing colocalized CtB and PACAP immunostaining were identified in the SCN, the lateral geniculate complex including the pregeniculate nucleus, the pretectal olivary nucleus, the nucleus of the optic tract, the brachium of the superior colliculus, and the superior colliculus. In conclusion, PACAP-immunoreactive projections with colocalized CtB represent retinal projections of ipRGCs in the macaque monkey, supporting previous retrograde tracer studies demonstrating that melanopsin-containing retinal projections reach areas in the primate brain involved in both image- and nonimage-forming visual processing.

| S-EPMC3996456 | biostudies-literature

Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse.

Project description:A subpopulation of retinal ganglion cells (RGCs) expresses the photopigment melanopsin, rendering these cells intrinsically photosensitive (ipRGCs). These cells are critical for competent circadian entrainment, pupillary light reflex, and other non-imaging-forming photic responses. Research has now demonstrated the presence of multiple subpopulations of ipRGC based on the dendritic stratification in the inner plexiform layer (IPL), those monostratified in the Off sublamina (M1), those monostratified in the On sublamina (M2,4,5), and those bistratified in both the On and the Off sublaminae (M3). Despite evidence that M1 and M2 cells are distinct subpopulations of ipRGC based on distinct morphological and physiological properties, the inclusion of M3 cells as a distinct subtype has remained controversial. Aside from the identification of M3 cells as a morphological subpopulation of ipRGC, to date there have been no functional descriptions of M3 cell physiology or synaptic inputs. Our data provide the first in-depth description of M3 cell structural and functional properties. We report that M3 cells form a morphologically heterogeneous population but one that is physiologically homogeneous with properties similar to those of M2 cells.

| S-EPMC3714856 | biostudies-literature

Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells.

Project description:Non-image-forming vision in mammals is mediated primarily by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, by far the best-studied subtype, melanopsin activates PLCβ4 (phospholipase C-β4) to open TRPC6,7 channels, mechanistically similar to phototransduction in fly rhabdomeric (microvillous) photoreceptors. We report here that, surprisingly, mouse M4-ipRGCs rely on a different and hitherto undescribed melanopsin-driven, ciliary phototransduction mechanism involving cyclic nucleotide as the second messenger and HCN channels rather than CNG channels as the ion channel for phototransduction. Even more surprisingly, within an individual mouse M2-ipRGC, this HCN-channel-dependent, ciliary phototransduction pathway operates in parallel with the TRPC6,7-dependent rhabdomeric pathway. These findings reveal a complex heterogeneity in phototransduction among ipRGCs and, more importantly, break a general dogma about segregation of the two phototransduction motifs, likely with strong evolutionary implications.

| S-EPMC6203304 | biostudies-literature

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