| First Author | Sterling JK | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 5 | Pages | 108271 |
| PubMed ID | 33147455 | Mgi Jnum | J:304496 |
| Mgi Id | MGI:6514506 | Doi | 10.1016/j.celrep.2020.108271 |
| Citation | Sterling JK, et al. (2020) GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension. Cell Rep 33(5):108271 |
| abstractText | Glaucoma is the leading cause of irreversible blindness and is characterized by the death of retinal ganglion cells (RGCs). Recent studies have implicated pro-inflammatory microglia, macrophages, and A1 astrocytes in the pathogenesis of neurodegenerative diseases. The role of pro-inflammatory, neurotoxic A1 astrocytes in glaucoma is just beginning to be explored. Using a mouse model of glaucoma, we demonstrate that ocular hypertension is sufficient to trigger production of C1q, interleukin-1alpha (IL-1alpha), and tumor necrosis factor alpha (TNF-alpha), three cytokines necessary and sufficient to drive the formation of A1 astrocytes. Upregulation of these cytokines occurs first in CD11b(+) CD11c(+) cells followed by CD11b(+) CD11c(-) cells. Ablation of this pathway, by either genetic deletions of C1qa, IL-1alpha, and TNF-alpha, or treatment with glucagon-like peptide-1 receptor agonist NLY01, reduces A1 astrocyte transformation and RGC death. Together, these results highlight a neuroinflammatory mechanism of glaucomatous neurodegeneration that can be therapeutically targeted by NLY01 administration. |
