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Immune Responses in the Glaucomatous Retina: Regulation and Dynamics

Glaucoma is a multifactorial disease resulting in progressive vision loss due to retinal ganglion cell (RGC) dysfunction and death. Early events in the pathobiology of the disease include oxidative, metabolic, or mechanical stress that acts upon RGC, causing these to rapidly release danger signals,...

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Autores principales: Shestopalov, Valery I., Spurlock, Markus, Gramlich, Oliver W., Kuehn, Markus H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391899/
https://www.ncbi.nlm.nih.gov/pubmed/34440742
http://dx.doi.org/10.3390/cells10081973
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author Shestopalov, Valery I.
Spurlock, Markus
Gramlich, Oliver W.
Kuehn, Markus H.
author_facet Shestopalov, Valery I.
Spurlock, Markus
Gramlich, Oliver W.
Kuehn, Markus H.
author_sort Shestopalov, Valery I.
collection PubMed
description Glaucoma is a multifactorial disease resulting in progressive vision loss due to retinal ganglion cell (RGC) dysfunction and death. Early events in the pathobiology of the disease include oxidative, metabolic, or mechanical stress that acts upon RGC, causing these to rapidly release danger signals, including extracellular ATP, resulting in micro- and macroglial activation and neuroinflammation. Danger signaling also leads to the formation of inflammasomes in the retina that enable maturation of proinflammatory cytokines such IL-1β and IL-18. Chronic neuroinflammation can have directly damaging effects on RGC, but it also creates a proinflammatory environment and compromises the immune privilege of the retina. In particular, continuous synthesis of proinflammatory mediators such as TNFα, IL-1β, and anaphylatoxins weakens the blood–retina barrier and recruits or activates T-cells. Recent data have demonstrated that adaptive immune responses strongly exacerbate RGC loss in animal models of the disease as T-cells appear to target heat shock proteins displayed on the surface of stressed RGC to cause their apoptotic death. It is possible that dysregulation of these immune responses contributes to the continued loss of RGC in some patients.
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spelling pubmed-83918992021-08-28 Immune Responses in the Glaucomatous Retina: Regulation and Dynamics Shestopalov, Valery I. Spurlock, Markus Gramlich, Oliver W. Kuehn, Markus H. Cells Review Glaucoma is a multifactorial disease resulting in progressive vision loss due to retinal ganglion cell (RGC) dysfunction and death. Early events in the pathobiology of the disease include oxidative, metabolic, or mechanical stress that acts upon RGC, causing these to rapidly release danger signals, including extracellular ATP, resulting in micro- and macroglial activation and neuroinflammation. Danger signaling also leads to the formation of inflammasomes in the retina that enable maturation of proinflammatory cytokines such IL-1β and IL-18. Chronic neuroinflammation can have directly damaging effects on RGC, but it also creates a proinflammatory environment and compromises the immune privilege of the retina. In particular, continuous synthesis of proinflammatory mediators such as TNFα, IL-1β, and anaphylatoxins weakens the blood–retina barrier and recruits or activates T-cells. Recent data have demonstrated that adaptive immune responses strongly exacerbate RGC loss in animal models of the disease as T-cells appear to target heat shock proteins displayed on the surface of stressed RGC to cause their apoptotic death. It is possible that dysregulation of these immune responses contributes to the continued loss of RGC in some patients. MDPI 2021-08-03 /pmc/articles/PMC8391899/ /pubmed/34440742 http://dx.doi.org/10.3390/cells10081973 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Shestopalov, Valery I.
Spurlock, Markus
Gramlich, Oliver W.
Kuehn, Markus H.
Immune Responses in the Glaucomatous Retina: Regulation and Dynamics
title Immune Responses in the Glaucomatous Retina: Regulation and Dynamics
title_full Immune Responses in the Glaucomatous Retina: Regulation and Dynamics
title_fullStr Immune Responses in the Glaucomatous Retina: Regulation and Dynamics
title_full_unstemmed Immune Responses in the Glaucomatous Retina: Regulation and Dynamics
title_short Immune Responses in the Glaucomatous Retina: Regulation and Dynamics
title_sort immune responses in the glaucomatous retina: regulation and dynamics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391899/
https://www.ncbi.nlm.nih.gov/pubmed/34440742
http://dx.doi.org/10.3390/cells10081973
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