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
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.
