| First Author | Passino R | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 3 | Pages | 113931 |
| PubMed ID | 38492223 | Mgi Jnum | J:348590 |
| Mgi Id | MGI:7616016 | Doi | 10.1016/j.celrep.2024.113931 |
| Citation | Passino R, et al. (2024) Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration. Cell Rep 43(3):113931 |
| abstractText | 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 beta-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to beta-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-alphaM), 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. |
