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GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension
- Source :
- Cell Reports, Vol 33, Iss 5, Pp 108271- (2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Summary: 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-1α (IL-1α), and tumor necrosis factor α (TNF-α), 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-1α, and TNF-α, 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.
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 33
- Issue :
- 5
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.75de906bdc0e4cc7bbdb65b3f0a09636
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.celrep.2020.108271