Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration
Summary: In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate β-glucan isolated from yeast. Blood-borne myeloid cells rapidly re...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724002596 |
| _version_ | 1797260328306737152 |
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| author | Ryan Passino Matthew C. Finneran Hannah Hafner Qian Feng Lucas D. Huffman Xiao-Feng Zhao Craig N. Johnson Riki Kawaguchi Juan A. Oses-Prieto Alma L. Burlingame Daniel H. Geschwind Larry I. Benowitz Roman J. Giger |
| author_facet | Ryan Passino Matthew C. Finneran Hannah Hafner Qian Feng Lucas D. Huffman Xiao-Feng Zhao Craig N. Johnson Riki Kawaguchi Juan A. Oses-Prieto Alma L. Burlingame Daniel H. Geschwind Larry I. Benowitz Roman J. Giger |
| author_sort | Ryan Passino |
| collection | DOAJ |
| description | Summary: In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate β-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to β-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q−/− or C3−/−, reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Together, these findings reveal that protection of the inflamed vasculature promotes neuronal regeneration. |
| first_indexed | 2024-04-24T23:23:34Z |
| format | Article |
| id | doaj.art-292ce40fd6534ad8ac191a8ef34cab42 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T23:23:34Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-292ce40fd6534ad8ac191a8ef34cab422024-03-16T05:08:18ZengElsevierCell Reports2211-12472024-03-01433113931Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regenerationRyan Passino0Matthew C. Finneran1Hannah Hafner2Qian Feng3Lucas D. Huffman4Xiao-Feng Zhao5Craig N. Johnson6Riki Kawaguchi7Juan A. Oses-Prieto8Alma L. Burlingame9Daniel H. Geschwind10Larry I. Benowitz11Roman J. Giger12Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartments of Psychiatry and Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USAUniversity of California San Francisco, Department of Pharmaceutical Chemistry, San Francisco, CA 94158, USAUniversity of California San Francisco, Department of Pharmaceutical Chemistry, San Francisco, CA 94158, USADepartments of Psychiatry and Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute of Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USADepartments of Neurosurgery and Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Department of Neurosurgery, Boston Children’s Hospital, Boston MA 02115, USA; Departmant of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USADepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Corresponding authorSummary: In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate β-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to β-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q−/− or C3−/−, reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Together, these findings reveal that protection of the inflamed vasculature promotes neuronal regeneration.http://www.sciencedirect.com/science/article/pii/S2211124724002596CP: Neuroscience |
| spellingShingle | Ryan Passino Matthew C. Finneran Hannah Hafner Qian Feng Lucas D. Huffman Xiao-Feng Zhao Craig N. Johnson Riki Kawaguchi Juan A. Oses-Prieto Alma L. Burlingame Daniel H. Geschwind Larry I. Benowitz Roman J. Giger Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration Cell Reports CP: Neuroscience |
| title | Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration |
| title_full | Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration |
| title_fullStr | Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration |
| title_full_unstemmed | Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration |
| title_short | Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration |
| title_sort | neutrophil inflicted vasculature damage suppresses immune mediated optic nerve regeneration |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724002596 |
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