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Mitogen-activated protein kinase-signaling regulates the ability of Müller glia to proliferate and protect retinal neurons against excitotoxicity
Open accessAbstract
The purpose of this study was to investigate whether insulin, fibroblast growth factor (FGF), and mitogen‐activated protein kinase (MAPK) pathways protect retinal neurons against excitotoxicity and regulate the proliferation of Müller glia. We found that intraocular injections of insulin or FGF2 had variable effects upon the phosphorylation of ERK1/2, p38 MAPK, and CREB, and the expression of immediate early genes, cFos and Egr1. Accumulations of pERK1/2, p38 MAPK, pCREB, cFos and Egr1 in response to insulin or FGF2 were confined to Müller glia, whereas retinal neurons did not seem to respond to growth factors. Unlike FGF2, insulin stimulated microglia‐like cells to upregulate the intermediate filament transitin and lysosomal membrane glycoprotein (LMG). With microglia‐like cells and Müller glia stimulated by insulin or FGF2 there were profound effects upon numbers of dying neurons in response to excitotoxic damage. Although FGF2 significantly reduced numbers of dying neurons, insulin significantly increased numbers of dying neurons. In addition to neuroprotective affects, FGF2 also “primed” the Müller glia to proliferate following retinal damage, whereas insulin had no effect upon glial proliferation. Further, we found that FGF receptor isoform 1 (FGFR1) and FGFR3 were prominently expressed in the retina, whereas the insulin receptor and FGFR2 are not expressed, or are expressed at very low levels. We conclude that MAPK‐signaling through FGF receptors stimulates Müller glia to become more neuroprotective and progenitor‐like, whereas insulin acting on Müller and microglia‐like cells through unidentified receptors had the opposite effect. © 2009 Wiley‐Liss, Inc.
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“Additionally, MG are primarily responsive to intra-ocular insulin with increased phosphorylation of ERK1/2 and p38 [ 77 ].”
From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [77]
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Citations
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Metadata
- Authors
- Fischer, A. J., Scott, M. A., Ritchey, E. R., & Sherwood, P.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Fischer, Andy J.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2009-03-20
- Volume
- 57
- Issue
- 14
- Pages
- 1538-1552
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- PMC
- PMC2775435
- OpenAlex
- W1998523437
- Cited by
- 111
- References
- 39
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 4 · 2017: 9 · 2016: 5 · 2015: 12 · 2014: 10 · 2013: 7 · 2012: 6
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (R01EY016043, EY016043)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- Müller cells, retinal neurons, excitotoxicity, neuroprotection, MAPK signaling, insulin, fibroblast growth factor 2, FGF receptor 1, FGF receptor 3, ERK1/2, p38 MAPK, CREB, c-fos, EGR1, microglia-like cells, lysosomal membrane glycoprotein, glial cell proliferation, retinal damage
- MeSH terms
- Animals, Chickens, Fibroblast Growth Factors, Insulin, Intermediate Filament Proteins, Nerve Tissue Proteins, Neuroglia, Neurotoxins, Phosphorylation, Retina, Signal Transduction, Proto-Oncogene Proteins c-fos, Cell Death, Cyclic AMP Response Element-Binding Protein, Receptors, Fibroblast Growth Factor, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Cell Proliferation, Early Growth Response Protein 1, Lysosomal Membrane Proteins, Retinal Neurons, Nestin
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