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GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension

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, neuro...

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Autores principales: Sterling, Jacob K., Adetunji, Modupe O., Guttha, Samyuktha, Bargoud, Albert R., Uyhazi, Katherine E., Ross, Ahmara G., Dunaief, Joshua L., Cui, Qi N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660987/
https://www.ncbi.nlm.nih.gov/pubmed/33147455
http://dx.doi.org/10.1016/j.celrep.2020.108271
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author Sterling, Jacob K.
Adetunji, Modupe O.
Guttha, Samyuktha
Bargoud, Albert R.
Uyhazi, Katherine E.
Ross, Ahmara G.
Dunaief, Joshua L.
Cui, Qi N.
author_facet Sterling, Jacob K.
Adetunji, Modupe O.
Guttha, Samyuktha
Bargoud, Albert R.
Uyhazi, Katherine E.
Ross, Ahmara G.
Dunaief, Joshua L.
Cui, Qi N.
author_sort Sterling, Jacob K.
collection PubMed
description 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.
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spelling pubmed-76609872020-11-12 GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension Sterling, Jacob K. Adetunji, Modupe O. Guttha, Samyuktha Bargoud, Albert R. Uyhazi, Katherine E. Ross, Ahmara G. Dunaief, Joshua L. Cui, Qi N. Cell Rep Article 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. 2020-11-03 /pmc/articles/PMC7660987/ /pubmed/33147455 http://dx.doi.org/10.1016/j.celrep.2020.108271 Text en This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sterling, Jacob K.
Adetunji, Modupe O.
Guttha, Samyuktha
Bargoud, Albert R.
Uyhazi, Katherine E.
Ross, Ahmara G.
Dunaief, Joshua L.
Cui, Qi N.
GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension
title GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension
title_full GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension
title_fullStr GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension
title_full_unstemmed GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension
title_short GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension
title_sort glp-1 receptor agonist nly01 reduces retinal inflammation and neuron death secondary to ocular hypertension
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660987/
https://www.ncbi.nlm.nih.gov/pubmed/33147455
http://dx.doi.org/10.1016/j.celrep.2020.108271
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