Cytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model

Glaucoma is a complex neurodegenerative disease leading to a loss of retinal ganglion cells (RGCs) and optic nerve axons. An activation of the complement system seems to contribute to cell loss in this disease. Hence, we investigated a possible initiation of the complement system and the cytokine re...

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Autores principales:	Sabrina Reinehr, Johanna D. Doerner, Ana M. Mueller-Buehl, Dennis Koch, Rudolf Fuchshofer, H. Burkhard Dick, Stephanie C. Joachim
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glaucoma βB1-CTGF complement system classical pathway CXCL1 cytokines Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/dcae5067634d4f8a89f80d14e5167502
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spelling	oai:doaj.org-article:dcae5067634d4f8a89f80d14e51675022021-11-18T08:02:18ZCytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model1662-510210.3389/fncel.2021.718087https://doaj.org/article/dcae5067634d4f8a89f80d14e51675022021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.718087/fullhttps://doaj.org/toc/1662-5102Glaucoma is a complex neurodegenerative disease leading to a loss of retinal ganglion cells (RGCs) and optic nerve axons. An activation of the complement system seems to contribute to cell loss in this disease. Hence, we investigated a possible initiation of the complement system and the cytokine response in the βB1-CTGF glaucoma model. In these mice, intraocular pressure is elevated, which is the main glaucoma risk factor in patients, and RGC loss occurs at 15 weeks of age. Therefore, quantitative real-time PCR and immunohistological experiments were performed in 5-, 10-, and 15-week-old βB1-CTGF animals and their corresponding wildtypes (WT) to analyze the expression of several complement system factors. We could show that mRNA levels of the terminal complement pathway components C3 and C5 (Hc) were upregulated at 10 weeks. In accordance, more C3+ and membrane attack complex+ cells were observed in transgenic retinae. Further, the C5a receptor anaphylatoxin receptor (C5ar) and the complement component C5a receptor 1 (C5ar1; CD88) mRNA levels were upregulated in 10- and 15-week-old βB1-CTGF mice. Interestingly, all three activation routes of the complement system were elevated in βB1-CTGF mice at some age. Especially C1q, as a marker of the classical pathway, was significantly increased at all investigated ages. Furthermore, mRNA expression levels of interferon-γ (Infg) were upregulated at 5 weeks, while Cxcl1 and Cxcl2 mRNA levels were upregulated at 10 and 15 weeks. The mRNA levels of the chemokines Cxcl10 were increased at all ages in βB1-CTGF mice. These results lead to the assumption that in these transgenic mice, a complement activation mainly through the classical pathway as well as a cytokine response plays a major role in cell death.Sabrina ReinehrJohanna D. DoernerAna M. Mueller-BuehlDennis KochRudolf FuchshoferH. Burkhard DickStephanie C. JoachimFrontiers Media S.A.articleglaucomaβB1-CTGFcomplement systemclassical pathwayCXCL1cytokinesNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glaucoma βB1-CTGF complement system classical pathway CXCL1 cytokines Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	glaucoma βB1-CTGF complement system classical pathway CXCL1 cytokines Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Sabrina Reinehr Johanna D. Doerner Ana M. Mueller-Buehl Dennis Koch Rudolf Fuchshofer H. Burkhard Dick Stephanie C. Joachim Cytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model
description	Glaucoma is a complex neurodegenerative disease leading to a loss of retinal ganglion cells (RGCs) and optic nerve axons. An activation of the complement system seems to contribute to cell loss in this disease. Hence, we investigated a possible initiation of the complement system and the cytokine response in the βB1-CTGF glaucoma model. In these mice, intraocular pressure is elevated, which is the main glaucoma risk factor in patients, and RGC loss occurs at 15 weeks of age. Therefore, quantitative real-time PCR and immunohistological experiments were performed in 5-, 10-, and 15-week-old βB1-CTGF animals and their corresponding wildtypes (WT) to analyze the expression of several complement system factors. We could show that mRNA levels of the terminal complement pathway components C3 and C5 (Hc) were upregulated at 10 weeks. In accordance, more C3+ and membrane attack complex+ cells were observed in transgenic retinae. Further, the C5a receptor anaphylatoxin receptor (C5ar) and the complement component C5a receptor 1 (C5ar1; CD88) mRNA levels were upregulated in 10- and 15-week-old βB1-CTGF mice. Interestingly, all three activation routes of the complement system were elevated in βB1-CTGF mice at some age. Especially C1q, as a marker of the classical pathway, was significantly increased at all investigated ages. Furthermore, mRNA expression levels of interferon-γ (Infg) were upregulated at 5 weeks, while Cxcl1 and Cxcl2 mRNA levels were upregulated at 10 and 15 weeks. The mRNA levels of the chemokines Cxcl10 were increased at all ages in βB1-CTGF mice. These results lead to the assumption that in these transgenic mice, a complement activation mainly through the classical pathway as well as a cytokine response plays a major role in cell death.
format	article
author	Sabrina Reinehr Johanna D. Doerner Ana M. Mueller-Buehl Dennis Koch Rudolf Fuchshofer H. Burkhard Dick Stephanie C. Joachim
author_facet	Sabrina Reinehr Johanna D. Doerner Ana M. Mueller-Buehl Dennis Koch Rudolf Fuchshofer H. Burkhard Dick Stephanie C. Joachim
author_sort	Sabrina Reinehr
title	Cytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model
title_short	Cytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model
title_full	Cytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model
title_fullStr	Cytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model
title_full_unstemmed	Cytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model
title_sort	cytokine and complement response in the glaucomatous βb1-ctgf mouse model
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/dcae5067634d4f8a89f80d14e5167502
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Cytokine and Complement Response in the Glaucomatous βB1-CTGF Mouse Model

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