Potential for neural regeneration after neurotoxic injury in the adult mammalian retina
Open accessAbstract
It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N -methyl- d -aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix–loop–helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.
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Mammalian Müller glia have only limited regenerative capacity under special conditions.
“they only exhibit a limited regenerative potential under special conditions”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Ooto et al., 2004
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- Authors
- Ooto, S., Akagi, T., Kageyama, R., Akita, J., Mandai, M., Honda, Y., & Takahashi, M.
- Affiliations
- Kyoto University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-09-07
- Volume
- 101
- Issue
- 37
- Pages
- 13654-13659
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC518808
- OpenAlex
- W2116718309
- Cited by
- 454
- References
- 39
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 12 · 2023: 13 · 2022: 14 · 2021: 20 · 2020: 17 · 2019: 25 · 2018: 23 · 2017: 32 · 2016: 26 · 2015: 30 · 2014: 20 · 2013: 26 · 2012: 24
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- retinal regeneration, Müller cells, NMDA neurotoxicity, bipolar cells, rod photoreceptors, retinoic acid, basic helix-loop-helix genes, homeobox genes, neuronal fate specification, retinal degeneration, gene therapy, drug delivery
- MeSH terms
- PAX6 Transcription Factor, Aging, Animals, Cell Differentiation, Cell Division, Eye Proteins, Gene Expression Regulation, Immunohistochemistry, Male, Nerve Regeneration, Nerve Tissue Proteins, Neuroglia, Neurons, Repressor Proteins, Retina, Rhodopsin, Tretinoin, Trans-Activators, N-Methylaspartate, Rats, Sprague-Dawley, Homeodomain Proteins, Rats, Paired Box Transcription Factors, Basic Helix-Loop-Helix Proteins
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