Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
Open accessAbstract
In zebrafish, Müller glia (MG) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision 1. In mammals, however, MG do not spontaneously re-enter the cell cycle to generate a population of stem or progenitor cells that differentiate into retinal neurons. Nevertheless, the regenerative machinery may exist in the mammalian retina, as retinal injury can stimulate MG proliferation followed by limited neurogenesis 2-7. Therefore, there is still a fundamental question regarding whether MG-derived regeneration can be exploited to restore vision in mammalian retinas. Gene transfer of β-catenin stimulates MG proliferation in the absence of injury in mouse retinas 8. Here we report that following gene transfer of β-catenin, cell-cycle-reactivated MG can be reprogrammed to generate rod photoreceptors by subsequent gene transfer of transcription factors essential for rod cell fate specification and determination. MG-derived rods restored visual responses in Gnat1 rd17 Gnat2 cpfl3 double mutant mice, a model of congenital blindness 9,10, throughout the visual pathway from the retina to the primary visual cortex. Together, our results provide evidence of vision restoration after de novo MG-derived genesis of rod photoreceptors in mammalian retinas.
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Gnat1 and 2 knockout mice lack expression of rod and cone α-transducin, respectively, and exhibit loss of signal transduction through these photoreceptors.
“Gnat1 and 2 knockout mice lack expression of rod and cone α-transducin, respectively, and exhibit loss of signal transduction through these photoreceptors (Deng et al., 2009; Yao et al., 2018).”
From Ventral striatum dopamine release encodes unique properties of visual stimuli in mice (2023) · cites this paper as Yao et al., 2018
The passage labeled Abstract says Gnat1rd17 mice lack rod α-transducin and that the double mutants lack photoreceptor-mediated light responses. It describes Gnat2cpfl3 mice as having *mutated* cone α-transducin, with poor cone responses by three weeks and none by nine weeks; it does not say they lack cone α-transducin expression. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMany regenerative approaches that work well in young individuals often fail in older ones.
“Many regenerative approaches that work well in young individuals often fail in older ones25,26.”
From Reprogramming to recover youthful epigenetic information and restore vision (2020) · cites this paper as [26]
The Abstract describes successful rod-photoreceptor regeneration in mature mouse retinas, with treatment beginning at four weeks of age. Our copy does not compare outcomes in young and older individuals or say that regenerative approaches often fail with age (searched: young versus older regeneration, age-dependent failure). (LLM, conf=0.76)
Experimental — accuracy not yet measuredMüller glia may be a target for gene therapy.
“Müller glia, which are the most abundant glial cells in the retina and play a multifaceted role in retinal homeostasis and response to injury, including potentially photoreceptor regeneration, may be a target for gene therapy [275,276].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [275]
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References 30 · Cited by 251
- Authors
- Yao, K., Qiu, S., Wang, Y. V., Park, S. J. H., Mohns, E. J., Mehta, B., Liu, X., Chang, B., Zenisek, D., Crair, M. C., Demb, J. B., & Chen, B.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Sun Yat-sen University (CN)
- Yale University (US)
- Jackson Laboratory (US)
- Corresponding author
- Chen, Bo
- ORCID
- Venue
- Nature
- Published
- 2018-08
- Volume
- 560
- Issue
- 7719
- Pages
- 484-488
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6107416
- OpenAlex
- W2885750548
- Cited by
- 251
- References
- 30
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 18 · 2023: 34 · 2022: 37 · 2021: 37 · 2020: 46 · 2019: 34 · 2018: 9 · 2014: 1
- FWCI
- 11.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- 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)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health (5r01ey019943-13)
- National Eye Institute (R01EY014454, R01EY023105, R01-EY019943, R01EY014990, R01EY021502, R01EY024986, R01EY021372, R01EY021195, R01EY015788, P30EY026878)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- Müller cells, rod photoreceptors, vision restoration, retinal regeneration, β-catenin, cell cycle re-entry, GNAT1, GNAT2, congenital blindness, retinal stem cells, transcription factors, primary visual cortex, mouse retina
- MeSH terms
- Animals, Blindness, Cell Cycle, Disease Models, Animal, Female, Male, Neuroglia, Stem Cells, Transcription Factors, Visual Cortex, Visual Pathways, Transducin, Retinal Rod Photoreceptor Cells, Heterotrimeric GTP-Binding Proteins, GTP-Binding Protein alpha Subunits, Regenerative Medicine, Cell Proliferation, beta Catenin, Mice, Neurogenesis, Cellular Reprogramming
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