ArticleProceedings of the National Academy of Sciences of the United States of America2021
Chemokine CCL5 promotes robust optic nerve regeneration and mediates many of the effects of CNTF gene therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The trial behind it
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Who cites it
49 citing papers in PubMed, 71 citations in OpenAlex.
- Mitochondrial Homeostasis Mediates the Sustained Neuroprotection of CNTF-Chitosan Hydrogel Against NMDA-Induced Retinal Ganglion Cell Excitotoxicity.International journal of molecular sciences · 2026Article
- Experimental upregulation of Lancl1 promotes axon regeneration after optic nerve injury in vivo.Experimental neurology · 2026Article
- The 5-HT1A receptor antagonist WAY-100635 maleate promotes retinal ganglion cell differentiation and protects the retino-visual circuits.Communications medicine · 2026Article
- From Regeneration Failure to Functional Restoration: Unlocking the Neuronal-Intrinsic Regenerative Capacity as a Therapeutic Frontier for Optic Neuropathy and Glaucoma.CNS neuroscience & therapeutics · 2026Review
- Conserved stromal EMT program controls regenerative capacity of mesenchymal stromal cells across multiple tissues.Science advances · 2026Article
- Modeling neurodegeneration in the retina and strategies for developing pan-neurodegenerative therapies.Molecular neurodegeneration · 2025Review
- Spatiotemporal Immune Dynamics in Experimental Retinal Ganglion Cell Injury Models.Immunity, inflammation and disease · 2025Review
- Transcriptomics of Various Diseases Reveals the Core Role of Immune System Pathways in Retinal Damage Repair and Nerve Regeneration.Molecular neurobiology · 2025Article
- Maraviroc Prevents Optic Nerve Injury-Induced Retinal Ganglion Cell Apoptosis by Modulating the CCL5/CCR5/CTSS Axis.Investigative ophthalmology & visual science · 2025Article
- TPEN loaded poly (lactide-co-glycolide) nanoparticles promote neuroprotection and optic nerve regeneration.Materials today. Bio · 2025Article
- The neuroimmune interface in retinal regeneration.Progress in retinal and eye research · 2025Review
- Evaluating the Evidence for Neuroprotective and Axonal Regenerative Activities of Different Inflammatory Cell Types After Optic Nerve Injury.Molecular neurobiology · 2025Review
- Review
- Exploring neuroglial signaling: diversity of molecules implicated in microglia-to-astrocyte neuroimmune communication.Reviews in the neurosciences · 2025Review
- Engineered bio-functional material-based nerve guide conduits for optic nerve regeneration: a view from the cellular perspective, challenges and the future outlook.Regenerative biomaterials · 2025Review
- Local glycolysis supports injury-induced axonal regeneration.The Journal of cell biology · 2024Article
- Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration.NPJ Regenerative medicine · 2024Article
- CCL5 is essential for axonogenesis and neuronal restoration after brain injury.Journal of biomedical science · 2024Article
- Activation of feedforward wiring in adult hippocampal neurons by the basic-helix-loop-helix transcription factor Ascl4.PNAS nexus · 2024Article
- Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo.Experimental neurology · 2024Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Ciliary neurotrophic factor (CNTF) is a leading therapeutic candidate for several ocular diseases and induces optic nerve regeneration in animal models. Paradoxically, however, although CNTF gene therapy promotes extensive regeneration, recombinant CNTF (rCNTF) has little effect. Because intraocular viral vectors induce inflammation, and because CNTF is an immune modulator, we investigated whether CNTF gene therapy acts indirectly through other immune mediators. The beneficial effects of CNTF gene therapy remained unchanged after deleting CNTF receptor alpha (CNTFRα) in retinal ganglion cells (RGCs), the projection neurons of the retina, but were diminished by depleting neutrophils or by genetically suppressing monocyte infiltration. CNTF gene therapy increased expression of C-C motif chemokine ligand 5 (CCL5) in immune cells and retinal glia, and recombinant CCL5 induced extensive axon regeneration. Conversely, CRISPR-mediated knockdown of the cognate receptor (CCR5) in RGCs or treating wild-type mice with a CCR5 antagonist repressed the effects of CNTF gene therapy. Thus, CCL5 is a previously unrecognized, potent activator of optic nerve regeneration and mediates many of the effects of CNTF gene therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.