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Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis
Glaucoma is a chronic optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) and the resulting mechanical stress are classically considered the main causes of RGC death. However, RGC degeneration and ensuing vision loss often...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177096/ https://www.ncbi.nlm.nih.gov/pubmed/37174673 http://dx.doi.org/10.3390/cells12091272 |
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author | Amato, Rosario Cammalleri, Maurizio Melecchi, Alberto Bagnoli, Paola Porciatti, Vittorio |
author_facet | Amato, Rosario Cammalleri, Maurizio Melecchi, Alberto Bagnoli, Paola Porciatti, Vittorio |
author_sort | Amato, Rosario |
collection | PubMed |
description | Glaucoma is a chronic optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) and the resulting mechanical stress are classically considered the main causes of RGC death. However, RGC degeneration and ensuing vision loss often occur independent of IOP, indicating a multifactorial nature of glaucoma, with the likely contribution of glial and vascular function. The aim of the present study was to provide a comprehensive evaluation of the time course of neuro–glial–vascular changes associated with glaucoma progression. We used DBA/2J mice in the age range of 2–15 months as a spontaneous model of glaucoma with progressive IOP elevation and RGC loss typical of human open-angle glaucoma. We found that the onset of RGC degeneration at 10 months of age coincided with that of IOP elevation and vascular changes such as decreased density, increased lacunarity and decreased tight-junction protein zonula occludens (ZO)-1, while hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were already significantly upregulated at 6 months of age together with the onset of Müller cell gliosis. Astrocytes, however, underwent significant gliosis at 10 months. These results indicate that Müller cell activation occurs well before IOP elevation, with probable inflammatory consequences, and represents an early event in the glaucomatous process. Early upregulation of HIF-1α and VEGF is likely to contribute to blood retinal barrier failure, facilitating RGC loss. The different time courses of neuro–glial–vascular changes during glaucoma progression provide further insight into the nature of the disease and suggest potential targets for the development of efficient therapeutic intervention aside from IOP lowering. |
format | Online Article Text |
id | pubmed-10177096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101770962023-05-13 Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis Amato, Rosario Cammalleri, Maurizio Melecchi, Alberto Bagnoli, Paola Porciatti, Vittorio Cells Article Glaucoma is a chronic optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) and the resulting mechanical stress are classically considered the main causes of RGC death. However, RGC degeneration and ensuing vision loss often occur independent of IOP, indicating a multifactorial nature of glaucoma, with the likely contribution of glial and vascular function. The aim of the present study was to provide a comprehensive evaluation of the time course of neuro–glial–vascular changes associated with glaucoma progression. We used DBA/2J mice in the age range of 2–15 months as a spontaneous model of glaucoma with progressive IOP elevation and RGC loss typical of human open-angle glaucoma. We found that the onset of RGC degeneration at 10 months of age coincided with that of IOP elevation and vascular changes such as decreased density, increased lacunarity and decreased tight-junction protein zonula occludens (ZO)-1, while hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were already significantly upregulated at 6 months of age together with the onset of Müller cell gliosis. Astrocytes, however, underwent significant gliosis at 10 months. These results indicate that Müller cell activation occurs well before IOP elevation, with probable inflammatory consequences, and represents an early event in the glaucomatous process. Early upregulation of HIF-1α and VEGF is likely to contribute to blood retinal barrier failure, facilitating RGC loss. The different time courses of neuro–glial–vascular changes during glaucoma progression provide further insight into the nature of the disease and suggest potential targets for the development of efficient therapeutic intervention aside from IOP lowering. MDPI 2023-04-27 /pmc/articles/PMC10177096/ /pubmed/37174673 http://dx.doi.org/10.3390/cells12091272 Text en © 2023 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 | Article Amato, Rosario Cammalleri, Maurizio Melecchi, Alberto Bagnoli, Paola Porciatti, Vittorio Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis |
title | Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis |
title_full | Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis |
title_fullStr | Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis |
title_full_unstemmed | Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis |
title_short | Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis |
title_sort | natural history of glaucoma progression in the dba/2j model: early contribution of müller cell gliosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177096/ https://www.ncbi.nlm.nih.gov/pubmed/37174673 http://dx.doi.org/10.3390/cells12091272 |
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