ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Cellular mechanisms associated with spontaneous and ciliary neurotrophic factor-cAMP-induced survival and axonal regeneration of adult retinal ganglion cells.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 168 citations in OpenAlex.
- Zebrafish optic nerve injury results in systemic retinal ganglion cell dedifferentiation.PLoS genetics · 2025Article
- In Vitro and In Vivo Methods for Studying Retinal Ganglion Cell Survival and Optic Nerve Regeneration.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Microglial cGAS-STING signaling underlies glaucoma pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Therapeutic and preventive effects of astaxanthin in ischemic stroke.Frontiers in nutrition · 2024Review
- Charcot-Marie-Tooth-1A and sciatic nerve crush rat models: insights from proteomics.Neural regeneration research · 2023Article
- Ciliary Neurotrophic Factor Derived From Astrocytes Protects Retinal Ganglion Cells Through PI3K/AKT, JAK/STAT, and MAPK/ERK Pathways.Investigative ophthalmology & visual science · 2022Article
- Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between Jak/Stat signaling and innate immune responses in the zebrafish retina.Development (Cambridge, England) · 2022Article
- Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art.Frontiers in pharmacology · 2022Review
- Agonist of growth hormone-releasing hormone enhances retinal ganglion cell protection induced by macrophages after optic nerve injury.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Microglia/Macrophages and CD4Frontiers in immunology · 2021Article
- Absence of axonal sprouting following unilateral lesion in 125-day-old rat supraoptic nucleus may be due to age-dependent decrease in protein levels of ciliary neurotrophic factor receptor alpha.The Journal of comparative neurology · 2019Article
- Article
- Role of neuritin in retinal ganglion cell death in adult mice following optic nerve injury.Scientific reports · 2018Article
- Neuroprotective Effects of Human Mesenchymal Stem Cells and Platelet-Derived Growth Factor on Human Retinal Ganglion Cells.Stem cells (Dayton, Ohio) · 2018Article
- Wound healing, cellular regeneration and plasticity: the elegans way.The International journal of developmental biology · 2018Review
- Polyaniline promotes peripheral nerve regeneration by enhancement of the brain‑derived neurotrophic factor and ciliary neurotrophic factor expression and activation of the ERK1/2/MAPK signaling pathway.Molecular medicine reports · 2017Article
- Sphingosine 1-Phosphate Receptor 1 Modulates CNTF-Induced Axonal Growth and Neuroprotection in the Mouse Visual System.Neural plasticity · 2017Article
- Virally delivered, constitutively active NFκB improves survival of injured retinal ganglion cells.The European journal of neuroscience · 2016Article
- Inhibition on Apoptosis Induced by Elevated Hydrostatic Pressure in Retinal Ganglion Cell-5 via Laminin Upregulating β1-integrin/Focal Adhesion Kinase/Protein Kinase B Signaling Pathway.Chinese medical journal · 2016Article
- Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells.Molecular neurobiology · 2015Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have shown previously that intraocular elevation of cAMP using the cAMP analog 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) failed to promote axonal regeneration of axotomized adult retinal ganglion cells (RGCs) into peripheral nerve (PN) grafts but significantly potentiated ciliary neurotrophic factor (CNTF)-induced axonal regeneration. Using the PN graft model, we now examine the mechanisms underlying spontaneous and CNTF/CPT-cAMP-induced neuronal survival and axonal regrowth. We found that blockade of the cAMP pathway executor protein kinase A (PKA) using the cell-permeable inhibitor KT5720 did not affect spontaneous survival and axonal regeneration but essentially abolished the CNTF/CPT-cAMP-induced RGC survival and axonal regeneration. Blockade of CNTF signaling pathways such as phosphotidylinositol 3-kinase (PI3K)/akt by 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) by 2-(2-diamino-3-methoxyphenyl-4H-1-benzopyran-4-one (PD98059), or Janus kinase (JAK)/signal transducer and activators of transcription (STAT3) by tyrphostin AG490 also blocked the CNTF/CPT-cAMP-dependent survival and regeneration effects. PKA activity assay and Western blots showed that KT5720, LY294002, and PD98059 almost completely inhibited PKA, PI3K/akt, and MAPK/ERK signal transduction, respectively, whereas AG490 substantially decreased JAK/STAT3 signal transduction. Intraocular injection of CPT-cAMP resulted in a small PKA-dependent increase in CNTF receptor alpha mRNA expression in the retinas, an effect that may facilitate CNTF action on survival and axonal regeneration. Surprisingly, in the absence of CNTF/CPT-cAMP, LY294002, PD98059, and AG490, but not KT5720, significantly enhanced spontaneous RGC survival, suggesting differential roles of these pathways in RGC survival under different conditions. Our data suggest that CNTF/CPT-cAMP-induced RGC survival and axonal regeneration are a result of multiple pathway actions, with PKA as an essential component, but that these pathways can function in an antagonistic manner under different conditions.
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