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Intrinsically Photosensitive Retinal Ganglion Cells of the Human Retina
Open accessAbstract
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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“When light enters the eye, it is detected by intrinsically photosensitive retinal ganglion cells, which then send signals to the suprachiasmatic nuclei in the hypothalamus, the brain's master clock that coordinates daily physiological rhythms [60].”
From Ocular light exposure interventions for sleep, circadian rhythms, rest-activity cycles, mood, and cognitive function in older adults: An Overview of Cochrane and non-Cochrane Systematic Reviews (2025) · cites this paper as [60]
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“The mechanism behind ocular light exposure interventions lies in the non‐image‐forming effects of light, mediated by specialised, intrinsically photosensitive retinal ganglion cell photoreceptors in the eye [60].”
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Metadata
- Authors
- Mure, L. S.
- Affiliations
- University of Bern (CH)
- Corresponding author
- Mure, Ludovic S.
- ORCID
- Mure, Ludovic S.
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2021-03-25
- Volume
- 12
- Pages
- 636330-636330
- ISSN
- 1664-2295 (ISSN-L)
- PMC
- PMC8027232
- OpenAlex
- W3151649762
- Cited by
- 151
- References
- 116
- Citations by year
- 2026: 32 · 2025: 31 · 2024: 27 · 2023: 37 · 2022: 19 · 2021: 5
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open Access CRIS of the University of Bern
- Funders
- University of Bern
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Keywords
- intrinsically photosensitive retinal ganglion cells, melanopsin, human retina, non-image-forming vision, circadian entrainment, pupillary light reflex, melatonin suppression, light perception, phototherapy
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