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An Alternative Pathway Mediates the Mouse and Human Cone Visual Cycle
Open accessAbstract
One of the fundamental mysteries of the human visual system is the continuous function of cone photoreceptors in bright daylight. As visual pigment is destroyed, or bleached, by light, cones require its rapid regeneration, which in turn involves rapid recycling of the pigment's chromophore. The canonical visual cycle for rod and cone pigments involves recycling of their chromophore from all-trans retinol to 11-cis retinal in the pigment epithelium, adjacent to photoreceptors. However, shortcomings of this pathway indicate the function of a second, cone-specific, mechanism for chromophore recycling. Indeed, biochemical and physiological studies on lower species have described a cone-specific visual cycle in addition to the long-known pigment epithelium pathway. Two important questions remain, however: what is the role of this pathway in the function of mammalian cones, and is it present in higher mammals, including humans? Here, we show that mouse, primate, and human neural retinas promote pigment regeneration and dark adaptation selectively in cones, but not in rods. This pathway supports rapid dark adaptation of mammalian cones and extends their dynamic range in background light independently of the pigment epithelium. This pigment-regeneration mechanism is essential for our daytime vision and appears to be evolutionarily conserved.
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“There is a second, so called cone visual cycle, that occurs in the Müller cells. It serves cones with fast recycling, necessary for their rapid dark adaptation and function in constant and bright illumination [29,47,59,60,61,62].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [61]
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Metadata
- Authors
- Wang, J.-S., & Kefalov, V. J.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Kefalov, Vladimir J.
- ORCID
- Kefalov, Vladimir J.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 19
- Issue
- 19
- Pages
- 1665-1669
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC2762012
- OpenAlex
- W2135946934
- Cited by
- 155
- References
- 28
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 10 · 2022: 3 · 2021: 8 · 2020: 11 · 2019: 18 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 17 · 2014: 9 · 2013: 7 · 2012: 8
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Research to Prevent Blindness
- National Institutes of Health
- National Eye Institute (EY 02687, P30EY002687, R01EY019312, EY019312)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- retinal regeneration, cone photoreceptors, dark adaptation, rod photoreceptors, pigment epithelium, 11-cis-retinal, all-trans-retinol, neural retina, evolutionary conservation, dynamic range
- MeSH terms
- Animals, Dark Adaptation, Electroretinography, Humans, Light, Retinal Pigments, Vision, Ocular, Vitamin A, Retinal Cone Photoreceptor Cells, Mice
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