M1 Intrinsically Photosensitive Retinal Ganglion Cells Integrate Rod and Melanopsin Inputs to Signal in Low Light

Lee, Seul Ki; Sonoda, Takuma; Schmidt, Tiffany M.

doi:10.1016/j.celrep.2019.11.024

Cited by 37 publications

(35 citation statements)

References 27 publications

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“…It is also important to note that despite the loss of rods and cones in rd/rd cl mice, a similar irradiance response range was apparent, and the irradiance required to generate a 50% response was the same for both genotypes. This demonstrates that although the rods and cones might contribute to phase shifting responses, the pRGCs can operate effectively on their own across the dynamic range of wildtype responses; indeed, a recent report suggests that pRGCs might be capable of detecting light at levels much dimmer than previously expected [ 53 ]. One possibility for the broad sensitivity range of pRGCs is that different pRGC populations, with different and overlapping sensitivity ranges, combine to provide sensitivity across an extended range of irradiances [ 54 ].…”

Section: The Discovery and Characterization Of The 3rd Retinal Phomentioning

confidence: 92%

Circadian Photoentrainment in Mice and Humans

Foster

Hughes

Peirson

2020

Biology

109

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Light around twilight provides the primary entrainment signal for circadian rhythms. Here we review the mechanisms and responses of the mouse and human circadian systems to light. Both utilize a network of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). In both species action spectra and functional expression of OPN4 in vitro show that melanopsin has a λmax close to 480 nm. Anatomical findings demonstrate that there are multiple pRGC sub-types, with some evidence in mice, but little in humans, regarding their roles in regulating physiology and behavior. Studies in mice, non-human primates and humans, show that rods and cones project to and can modulate the light responses of pRGCs. Such an integration of signals enables the rods to detect dim light, the cones to detect higher light intensities and the integration of intermittent light exposure, whilst melanopsin measures bright light over extended periods of time. Although photoreceptor mechanisms are similar, sensitivity thresholds differ markedly between mice and humans. Mice can entrain to light at approximately 1 lux for a few minutes, whilst humans require light at high irradiance (>100’s lux) and of a long duration (>30 min). The basis for this difference remains unclear. As our retinal light exposure is highly dynamic, and because photoreceptor interactions are complex and difficult to model, attempts to develop evidence-based lighting to enhance human circadian entrainment are very challenging. A way forward will be to define human circadian responses to artificial and natural light in the “real world” where light intensity, duration, spectral quality, time of day, light history and age can each be assessed.

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Section: The Discovery and Characterization Of The 3rd Retinal Phomentioning

confidence: 92%

Circadian Photoentrainment in Mice and Humans

Foster

Hughes

Peirson

2020

Biology

109

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“…In a similar way to conventional RGCs, ipRGCs convey rod- and cone-initiated photoresponses and integrate these extrinsic signals and their intrinsic photosensitivity ( 80 , 81 ). The contribution of outer retina photoreceptors to human ipRGC signaling can be studied by comparing ipRGC responses before and after application of synaptic blockers that isolate RGCs from extrinsic input ( 55 ) ( Figure 3 ).…”

Section: Integration Of External Input From Photoreceptorsmentioning

confidence: 99%

Intrinsically Photosensitive Retinal Ganglion Cells of the Human Retina

Mure

2021

Front. Neurol.

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Light profoundly affects our mental and physical health. In particular, light, when not delivered at the appropriate time, may have detrimental effects. In mammals, light is perceived not only by rods and cones but also by a subset of retinal ganglion cells that express the photopigment melanopsin that renders them intrinsically photosensitive (ipRGCs). ipRGCs participate in contrast detection and play critical roles in non-image-forming vision, a set of light responses that include circadian entrainment, pupillary light reflex (PLR), and the modulation of sleep/alertness, and mood. ipRGCs are also found in the human retina, and their response to light has been characterized indirectly through the suppression of nocturnal melatonin and PLR. However, until recently, human ipRGCs had rarely been investigated directly. This gap is progressively being filled as, over the last years, an increasing number of studies provided descriptions of their morphology, responses to light, and gene expression. Here, I review the progress in our knowledge of human ipRGCs, in particular, the different morphological and functional subtypes described so far and how they match the murine subtypes. I also highlight questions that remain to be addressed. Investigating ipRGCs is critical as these few cells play a major role in our well-being. Additionally, as ipRGCs display increased vulnerability or resilience to certain disorders compared to conventional RGCs, a deeper knowledge of their function could help identify therapeutic approaches or develop diagnostic tools. Overall, a better understanding of how light is perceived by the human eye will help deliver precise light usage recommendations and implement light-based therapeutic interventions to improve cognitive performance, mood, and life quality.

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“…Melanopsin has long been thought to be relatively insensitive to light (but see Lee et al, 2019) and cannot induce pupil constriction when it is the only functioning photoreceptor except in very bright light (Keenan et al, 2016;Lucas et al, 2001). Surprisingly, we find that melanopsin drives an incredibly slow pupil constriction at scotopic light levels in mGluR6 KO animals ( Figure 3A).…”

Section: A Dramatically Slow Plr At Scotopic Levels Depends On the Sementioning

confidence: 44%

Retinal circuits driving a non-image forming visual behavior

Beier

Bocchero²,

Zhang

et al. 2020

Preprint

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Outer retinal circuits that drive non-image forming vision in mammals are unknown. Rods and cones signal light increments and decrements to the brain through the ON and OFF pathways, respectively. Although their contribution to image-forming vision is known, the contributions of the ON and OFF pathway to the pupillary light response (PLR), a non-image forming behavior, are unexplored. Here we use genetically modified mouse lines, to comprehensively define the outer retinal circuits driving the PLR. The OFF pathway, which mirrors the ON pathway in image-forming vision, plays no role in the PLR. We found that rods use the primary rod pathway to drive the PLR at scotopic light levels. At photopic light levels, the primary and secondary rod pathways drive normal PLR. Importantly, we find that cones are unable to compensate for rods. Thus, retinal circuit dynamics allow rods to drive the PLR across a wide range of light intensities.

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M1 Intrinsically Photosensitive Retinal Ganglion Cells Integrate Rod and Melanopsin Inputs to Signal in Low Light

Cited by 37 publications

References 27 publications

Circadian Photoentrainment in Mice and Humans

Circadian Photoentrainment in Mice and Humans

Intrinsically Photosensitive Retinal Ganglion Cells of the Human Retina

Retinal circuits driving a non-image forming visual behavior

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