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Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients

Neuroinflammation is recognized as a key component of neurodegenerative disease. In glaucoma, a common neurodegenerative disease and the leading cause of irreversible blindness, the evidence for neuroinflammation in patients is lacking. Animal models have demonstrated significant pro-inflammatory ac...

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Autores principales: Rutigliani, Carola, Tribble, James R., Hagström, Anna, Lardner, Emma, Jóhannesson, Gauti, Stålhammar, Gustav, Williams, Pete A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392254/
https://www.ncbi.nlm.nih.gov/pubmed/35986368
http://dx.doi.org/10.1186/s40478-022-01427-3
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author Rutigliani, Carola
Tribble, James R.
Hagström, Anna
Lardner, Emma
Jóhannesson, Gauti
Stålhammar, Gustav
Williams, Pete A.
author_facet Rutigliani, Carola
Tribble, James R.
Hagström, Anna
Lardner, Emma
Jóhannesson, Gauti
Stålhammar, Gustav
Williams, Pete A.
author_sort Rutigliani, Carola
collection PubMed
description Neuroinflammation is recognized as a key component of neurodegenerative disease. In glaucoma, a common neurodegenerative disease and the leading cause of irreversible blindness, the evidence for neuroinflammation in patients is lacking. Animal models have demonstrated significant pro-inflammatory activation of resident glia in the retina, as well as influx of blood-derived monocytes and pro-inflammatory factors. Confirmation of this in human donor tissue has been challenging due to a lack of well-preserved and well-characterized post-mortem tissue. To address this we utilize archived, wax embedded eyes fixed immediately following enucleation from living glaucoma patients. We compared glaucoma to control eyes (enucleated for uveal melanoma where the tumor did not impact the central retina or optic nerve). We performed immunolabelling for neurodegenerative and glial markers (CD45, CD163, IBA1, GFAP, Vimentin) which were quantified by high-resolution light microscopy and image analysis in FIJI. Glaucoma eyes demonstrated significant neural loss consistent with advanced neurodegeneration. IBA1 and GFAP were significantly increased in the retina and optic nerve head of the glaucomatous eyes indicating that significant neuroinflammation had occurred which support findings in animal models. Inflammation is a treatable symptom of many diseases and as such, identification of earlier inflammatory processes in glaucoma could be important for potential future treatment options. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01427-3.
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spelling pubmed-93922542022-08-21 Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients Rutigliani, Carola Tribble, James R. Hagström, Anna Lardner, Emma Jóhannesson, Gauti Stålhammar, Gustav Williams, Pete A. Acta Neuropathol Commun Research Neuroinflammation is recognized as a key component of neurodegenerative disease. In glaucoma, a common neurodegenerative disease and the leading cause of irreversible blindness, the evidence for neuroinflammation in patients is lacking. Animal models have demonstrated significant pro-inflammatory activation of resident glia in the retina, as well as influx of blood-derived monocytes and pro-inflammatory factors. Confirmation of this in human donor tissue has been challenging due to a lack of well-preserved and well-characterized post-mortem tissue. To address this we utilize archived, wax embedded eyes fixed immediately following enucleation from living glaucoma patients. We compared glaucoma to control eyes (enucleated for uveal melanoma where the tumor did not impact the central retina or optic nerve). We performed immunolabelling for neurodegenerative and glial markers (CD45, CD163, IBA1, GFAP, Vimentin) which were quantified by high-resolution light microscopy and image analysis in FIJI. Glaucoma eyes demonstrated significant neural loss consistent with advanced neurodegeneration. IBA1 and GFAP were significantly increased in the retina and optic nerve head of the glaucomatous eyes indicating that significant neuroinflammation had occurred which support findings in animal models. Inflammation is a treatable symptom of many diseases and as such, identification of earlier inflammatory processes in glaucoma could be important for potential future treatment options. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01427-3. BioMed Central 2022-08-19 /pmc/articles/PMC9392254/ /pubmed/35986368 http://dx.doi.org/10.1186/s40478-022-01427-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Rutigliani, Carola
Tribble, James R.
Hagström, Anna
Lardner, Emma
Jóhannesson, Gauti
Stålhammar, Gustav
Williams, Pete A.
Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients
title Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients
title_full Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients
title_fullStr Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients
title_full_unstemmed Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients
title_short Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients
title_sort widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392254/
https://www.ncbi.nlm.nih.gov/pubmed/35986368
http://dx.doi.org/10.1186/s40478-022-01427-3
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