GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension
| العنوان: | GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension |
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| المؤلفون: | Samyuktha Guttha, Ahmara G. Ross, Albert Bargoud, Joshua L. Dunaief, Katherine E. Uyhazi, Qi N. Cui, Jacob Sterling, Modupe O Adetunji |
| المصدر: | Cell reports Cell Reports, Vol 33, Iss 5, Pp 108271-(2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Agonist, Male, Retinal Ganglion Cells, medicine.drug_class, A1 reactive astrocyte, Retinal ganglion, General Biochemistry, Genetics and Molecular Biology, Glucagon-Like Peptide-1 Receptor, Article, neuroinflammation, 03 medical and health sciences, 0302 clinical medicine, Interleukin-1alpha, medicine, Animals, retinal ganglion cell, lcsh:QH301-705.5, Neuroinflammation, Intraocular Pressure, Inflammation, CD11b Antigen, Microglia, Cell Death, business.industry, Tumor Necrosis Factor-alpha, Complement C1q, Neurodegeneration, medicine.disease, NLY01, Astrogliosis, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, glaucoma, Retinal ganglion cell, lcsh:Biology (General), Astrocytes, Cancer research, Female, Ocular Hypertension, sense organs, Neuron death, business, 030217 neurology & neurosurgery, Retinal Neurons |
| الوصف: | 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. Graphical Abstract In Brief Sterling et al. show that in response to ocular hypertension, CD11b+ CD11c+ cells contribute to early retinal inflammation and astrogliosis in a mouse model of glaucoma. Ablation of this inflammatory pathway, via genetic deletion or administration of the GLP-1R agonist NLY01, prevents astrogliosis and retinal ganglion cell death. |
| تدمد: | 2211-1247 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aefbbe4473e0fef67bbd9ae0a48e5acaTest https://pubmed.ncbi.nlm.nih.gov/33147455Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....aefbbe4473e0fef67bbd9ae0a48e5aca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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