Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration

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

Cell Reports (Mar 2024)

Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration

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

Affiliations

Ryan Passino: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Matthew C. Finneran: Department 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
Hannah Hafner: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Qian Feng: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Lucas D. Huffman: Department 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
Xiao-Feng Zhao: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Craig N. Johnson: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Riki Kawaguchi: Departments 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, USA
Juan A. Oses-Prieto: University of California San Francisco, Department of Pharmaceutical Chemistry, San Francisco, CA 94158, USA
Alma L. Burlingame: University of California San Francisco, Department of Pharmaceutical Chemistry, San Francisco, CA 94158, USA
Daniel H. Geschwind: Departments 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, USA
Larry I. Benowitz: Departments 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, USA
Roman J. Giger: Department 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 author

Journal volume & issue: Vol. 43, no. 3
p. 113931

Abstract

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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.

CP: Neuroscience

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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