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A direct and melanopsin-dependent fetal light response regulates mouse eye development
Open accessAbstract
Vascular patterning is critical for organ function. In the eye, there is simultaneous regression of embryonic hyaloid vasculature (important to clear the optical path) and formation of the retinal vasculature (important for the high metabolic demands of retinal neurons). These events occur postnatally in the mouse. Here we have identified a light-response pathway that regulates both processes. We show that when mice are mutated in the gene (Opn4) for the atypical opsin melanopsin, or are dark-reared from late gestation, the hyaloid vessels are persistent at 8 days post-partum and the retinal vasculature overgrows. We provide evidence that these vascular anomalies are explained by a light-response pathway that suppresses retinal neuron number, limits hypoxia and, as a consequence, holds local expression of vascular endothelial growth factor (VEGFA) in check. We also show that the light response for this pathway occurs in late gestation at about embryonic day 16 and requires the photopigment in the fetus and not the mother. Measurements show that visceral cavity photon flux is probably sufficient to activate melanopsin-expressing retinal ganglion cells in the mouse fetus. These data thus show that light--the stimulus for function of the mature eye--is also critical in preparing the eye for vision by regulating retinal neuron number and initiating a series of events that ultimately pattern the ocular blood vessels.
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“As fetuses develop, they become sensitive to light cues penetrating through the mother’s abdomen59.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [59]
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Metadata
- Authors
- Rao, S., Chun, C., Fan, J., Kofron, J. M., Yang, M. B., Hegde, R. S., Ferrara, N., Copenhagen, D. R., & Lang, R. A.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of California, San Francisco (US)
- Genentech (US)
- Corresponding author
- Copenhagen, David R.
- Lang, Richard A.
- ORCID
- Venue
- Nature
- Published
- 2013-01-16
- Volume
- 494
- Issue
- 7436
- Pages
- 243-246
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3746810
- OpenAlex
- W2088406510
- Cited by
- 240
- References
- 31
- Citations by year
- 2026: 22 · 2025: 21 · 2024: 19 · 2023: 22 · 2022: 15 · 2021: 14 · 2020: 15 · 2019: 11 · 2018: 17 · 2017: 21 · 2016: 15 · 2015: 21 · 2014: 17 · 2013: 10
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Eye Institute (R01EY022917, R01EY021636, R01EY014648, R01EY023179, R01EY001869)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR47363, P30AR047363)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinopathy of Prematurity Studies
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- melanopsin, retinal angiogenesis, retinal vasculature development, VEGF-A, retinal ganglion cells, photoreceptors, hypoxia, eye development, vascular patterning
- MeSH terms
- Melanopsin, Animals, Cell Count, Eye, Female, Fetus, Light, Mice, Inbred C57BL, Neovascularization, Pathologic, Retinal Ganglion Cells, Cell Hypoxia, Rod Opsins, Photons, Neovascularization, Physiologic, Vascular Endothelial Growth Factor A, Mice, Retinal Neurons, Light Signal Transduction
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