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Preservation of optic nerve structure by complement inhibition in experimental glaucoma

Glaucoma is characterized by a progressive damage of the retina and the optic nerve. Despite a huge research interest, the exact pathomechanisms are still unknown. In the experimental autoimmune glaucoma model, rats develop glaucoma-like damage of the retina and the optic nerve after immunization wi...

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Autores principales: Gassel, Caroline J., Reinehr, Sabrina, Gomes, Sara C., Dick, H. Burkhard, Joachim, Stephanie C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285355/
https://www.ncbi.nlm.nih.gov/pubmed/32676862
http://dx.doi.org/10.1007/s00441-020-03240-7
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author Gassel, Caroline J.
Reinehr, Sabrina
Gomes, Sara C.
Dick, H. Burkhard
Joachim, Stephanie C.
author_facet Gassel, Caroline J.
Reinehr, Sabrina
Gomes, Sara C.
Dick, H. Burkhard
Joachim, Stephanie C.
author_sort Gassel, Caroline J.
collection PubMed
description Glaucoma is characterized by a progressive damage of the retina and the optic nerve. Despite a huge research interest, the exact pathomechanisms are still unknown. In the experimental autoimmune glaucoma model, rats develop glaucoma-like damage of the retina and the optic nerve after immunization with an optic nerve antigen homogenate (ONA). An early activation of the complement system, even before optic nerve degeneration, was reported in this model. Here, we investigated the effects of a monoclonal antibody against complement factor C5 on optic nerves. Rats were immunized with ONA and compared to controls. In one eye of some ONA animals, the antibody against C5 was intravitreally injected (15 μmol: ONA + C5-I or 25 μmol: ONA + C5-II) before immunization and then every 2 weeks. After 6 weeks, optic nerves were processed for histology (n = 6/group). These analyses demonstrated that the intravitreal therapy reduced the depositions of the membrane attack complex compared to ONA animals (ONA + C5-I: p = 0.005; ONA + C5-II: p = 0.002). Cellular infiltration was significantly reduced in the ONA + C5-I group (p = 0.003), but not in ONA + C5-II tissues (p = 0.41). Furthermore, SMI-32 staining revealed that neurofilament was preserved in both treatment groups compared to ONA optic nerves (both p = 0.002). A decreased amount of microglia was found in treated animals in comparison to the ONA group (ONA + C5-I: p = 0.03; ONA + C5-II: p = 0.009). We observed, for the first time, that a complement system inhibition could prevent optic nerve damage in an autoimmune glaucoma model. Therefore, complement inhibition could serve as a new therapeutic tool for glaucoma.
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spelling pubmed-82853552021-07-20 Preservation of optic nerve structure by complement inhibition in experimental glaucoma Gassel, Caroline J. Reinehr, Sabrina Gomes, Sara C. Dick, H. Burkhard Joachim, Stephanie C. Cell Tissue Res Regular Article Glaucoma is characterized by a progressive damage of the retina and the optic nerve. Despite a huge research interest, the exact pathomechanisms are still unknown. In the experimental autoimmune glaucoma model, rats develop glaucoma-like damage of the retina and the optic nerve after immunization with an optic nerve antigen homogenate (ONA). An early activation of the complement system, even before optic nerve degeneration, was reported in this model. Here, we investigated the effects of a monoclonal antibody against complement factor C5 on optic nerves. Rats were immunized with ONA and compared to controls. In one eye of some ONA animals, the antibody against C5 was intravitreally injected (15 μmol: ONA + C5-I or 25 μmol: ONA + C5-II) before immunization and then every 2 weeks. After 6 weeks, optic nerves were processed for histology (n = 6/group). These analyses demonstrated that the intravitreal therapy reduced the depositions of the membrane attack complex compared to ONA animals (ONA + C5-I: p = 0.005; ONA + C5-II: p = 0.002). Cellular infiltration was significantly reduced in the ONA + C5-I group (p = 0.003), but not in ONA + C5-II tissues (p = 0.41). Furthermore, SMI-32 staining revealed that neurofilament was preserved in both treatment groups compared to ONA optic nerves (both p = 0.002). A decreased amount of microglia was found in treated animals in comparison to the ONA group (ONA + C5-I: p = 0.03; ONA + C5-II: p = 0.009). We observed, for the first time, that a complement system inhibition could prevent optic nerve damage in an autoimmune glaucoma model. Therefore, complement inhibition could serve as a new therapeutic tool for glaucoma. Springer Berlin Heidelberg 2020-07-17 2020 /pmc/articles/PMC8285355/ /pubmed/32676862 http://dx.doi.org/10.1007/s00441-020-03240-7 Text en © The Author(s) 2020, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) .
spellingShingle Regular Article
Gassel, Caroline J.
Reinehr, Sabrina
Gomes, Sara C.
Dick, H. Burkhard
Joachim, Stephanie C.
Preservation of optic nerve structure by complement inhibition in experimental glaucoma
title Preservation of optic nerve structure by complement inhibition in experimental glaucoma
title_full Preservation of optic nerve structure by complement inhibition in experimental glaucoma
title_fullStr Preservation of optic nerve structure by complement inhibition in experimental glaucoma
title_full_unstemmed Preservation of optic nerve structure by complement inhibition in experimental glaucoma
title_short Preservation of optic nerve structure by complement inhibition in experimental glaucoma
title_sort preservation of optic nerve structure by complement inhibition in experimental glaucoma
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285355/
https://www.ncbi.nlm.nih.gov/pubmed/32676862
http://dx.doi.org/10.1007/s00441-020-03240-7
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