Stimulation of neural regeneration in the mouse retina
Open accessAbstract
Müller glia can serve as a source of new neurons after retinal damage in both fish and birds. Investigations of regeneration in the mammalian retina in vitro have provided some evidence that Müller glia can proliferate after retinal damage and generate new rods; however, the evidence that this occurs in vivo is not conclusive. We have investigated whether Müller glia have the potential to generate neurons in the mouse retina in vivo by eliminating ganglion and amacrine cells with intraocular NMDA injections and stimulating Müller glial to re-enter the mitotic cycle by treatment with specific growth factors. The proliferating Müller glia dedifferentiate and a subset of these cells differentiated into amacrine cells, as defined by the expression of amacrine cell-specific markers Calretinin, NeuN, Prox1, and GAD67-GFP. These results show for the first time that the mammalian retina has the potential to regenerate inner retinal neurons in vivo .
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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 Karl et al., 2008
EGF stimulation of injured mouse retina did not induce Ascl1 gene expression.
“Indeed, EGF stimulation of the injured mouse retina did not induce Ascl1 gene expression (Karl et al., 2008), which is an essential regeneration-associated gene in zebrafish (Fausett et al., 2008; Ramachandran et al., 2010a).”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Karl et al., 2008
Even in damaged mouse retina with induced EGFR, regeneration was limited to a small number of amacrine cells.
“However, even in the damaged mouse retina where EGFR was induced, regeneration was restricted to a small number of amacrine cells (Karl et al., 2008).”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Karl et al., 2008
EGF treatment did not stimulate Müller glia proliferation in mouse retina unless the retina was also damaged.
“Interestingly, EGF treatment of the mouse retina did not stimulate MG proliferation unless retinas were also damaged (Karl et al., 2008).”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Karl et al., 2008
MAPK signaling likely mediates EGF effects on Müller glia proliferation in injured mouse retina.
“MAPK signaling was previously reported to be required for proliferation of MG-derived progenitors in the postnatal chick retina (Fischer et al., 2009a; Fischer et al., 2009b) and likely mediates the effects of EGF on MG proliferation in the injured mouse retina (Karl et al., 2008).”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Karl et al., 2008
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BackgroundInfluentialRestoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
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- Authors
- Karl, M. O., Hayes, S., Nelson, B. R., Tan, K., Buckingham, B., & Reh, T. A.
- Affiliations
- Department of Biological Structure, and
- University of Washington (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-12-09
- Volume
- 105
- Issue
- 49
- Pages
- 19508-19513
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2614791
- OpenAlex
- W2116869556
- Cited by
- 368
- References
- 39
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 14 · 2023: 21 · 2022: 24 · 2021: 25 · 2020: 19 · 2019: 20 · 2018: 27 · 2017: 25 · 2016: 22 · 2015: 25 · 2014: 21 · 2013: 23 · 2012: 22
- FWCI
- 7.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- Deutsche Forschungsgemeinschaft
- National Eye Institute (R01EY013475, F32EY016636, F32EY015631, F32 EY15631-01A1)
- 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, amacrine cells, retinal ganglion cells, neuronal proliferation, growth factors, calretinin, Prox1, GAD67, mouse retina
- MeSH terms
- Prospero-Related Homeobox 1 Protein, Animals, Cell Differentiation, Cell Division, Denervation, DNA-Binding Proteins, Glutamate Decarboxylase, Mice, Transgenic, Nerve Regeneration, Nerve Tissue Proteins, Neuroglia, Neurons, Nuclear Proteins, Retina, Biomarkers, N-Methylaspartate, Homeodomain Proteins, Excitatory Amino Acid Agonists, Cell Lineage, Amacrine Cells, Tumor Suppressor Proteins, Green Fluorescent Proteins, Mice, S100 Calcium Binding Protein G, Calbindin 2
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