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Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas

Considering the fact that many retinal diseases are yet to be cured, the pathomechanisms of these multifactorial diseases need to be investigated in more detail. Among others, oxidative stress and hypoxia are pathomechanisms that take place in retinal diseases, such as glaucoma, age-related macular...

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Autores principales: Mueller-Buehl, Ana M., Buehner, Torsten, Pfarrer, Christiane, Deppe, Leonie, Peters, Laura, Dick, Burkhard H., Joachim, Stephanie C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700265/
https://www.ncbi.nlm.nih.gov/pubmed/34944083
http://dx.doi.org/10.3390/cells10123575
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author Mueller-Buehl, Ana M.
Buehner, Torsten
Pfarrer, Christiane
Deppe, Leonie
Peters, Laura
Dick, Burkhard H.
Joachim, Stephanie C.
author_facet Mueller-Buehl, Ana M.
Buehner, Torsten
Pfarrer, Christiane
Deppe, Leonie
Peters, Laura
Dick, Burkhard H.
Joachim, Stephanie C.
author_sort Mueller-Buehl, Ana M.
collection PubMed
description Considering the fact that many retinal diseases are yet to be cured, the pathomechanisms of these multifactorial diseases need to be investigated in more detail. Among others, oxidative stress and hypoxia are pathomechanisms that take place in retinal diseases, such as glaucoma, age-related macular degeneration, or diabetic retinopathy. In consideration of these diseases, it is also evidenced that the immune system, including the complement system and its activation, plays an important role. Suitable models to investigate neuroretinal diseases are organ cultures of porcine retina. Based on an established model, the role of the complement system was studied after the induction of oxidative stress or hypoxia. Both stressors led to a loss of retinal ganglion cells (RGCs) accompanied by apoptosis. Hypoxia activated the complement system as noted by higher C3(+) and MAC(+) cell numbers. In this model, activation of the complement cascade occurred via the classical pathway and the number of C1q(+) microglia was increased. In oxidative stressed retinas, the complement system had no consideration, but strong inflammation took place, with elevated TNF, IL6, and IL8 mRNA expression levels. Together, this study shows that hypoxia and oxidative stress induce different mechanisms in the porcine retina inducing either the immune response or an inflammation. Our findings support the thesis that the immune system is involved in the development of retinal diseases. Furthermore, this study is evidence that both approaches seem suitable models to investigate undergoing pathomechanisms of several neuroretinal diseases.
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spelling pubmed-87002652021-12-24 Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas Mueller-Buehl, Ana M. Buehner, Torsten Pfarrer, Christiane Deppe, Leonie Peters, Laura Dick, Burkhard H. Joachim, Stephanie C. Cells Article Considering the fact that many retinal diseases are yet to be cured, the pathomechanisms of these multifactorial diseases need to be investigated in more detail. Among others, oxidative stress and hypoxia are pathomechanisms that take place in retinal diseases, such as glaucoma, age-related macular degeneration, or diabetic retinopathy. In consideration of these diseases, it is also evidenced that the immune system, including the complement system and its activation, plays an important role. Suitable models to investigate neuroretinal diseases are organ cultures of porcine retina. Based on an established model, the role of the complement system was studied after the induction of oxidative stress or hypoxia. Both stressors led to a loss of retinal ganglion cells (RGCs) accompanied by apoptosis. Hypoxia activated the complement system as noted by higher C3(+) and MAC(+) cell numbers. In this model, activation of the complement cascade occurred via the classical pathway and the number of C1q(+) microglia was increased. In oxidative stressed retinas, the complement system had no consideration, but strong inflammation took place, with elevated TNF, IL6, and IL8 mRNA expression levels. Together, this study shows that hypoxia and oxidative stress induce different mechanisms in the porcine retina inducing either the immune response or an inflammation. Our findings support the thesis that the immune system is involved in the development of retinal diseases. Furthermore, this study is evidence that both approaches seem suitable models to investigate undergoing pathomechanisms of several neuroretinal diseases. MDPI 2021-12-18 /pmc/articles/PMC8700265/ /pubmed/34944083 http://dx.doi.org/10.3390/cells10123575 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 Article
Mueller-Buehl, Ana M.
Buehner, Torsten
Pfarrer, Christiane
Deppe, Leonie
Peters, Laura
Dick, Burkhard H.
Joachim, Stephanie C.
Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas
title Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas
title_full Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas
title_fullStr Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas
title_full_unstemmed Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas
title_short Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas
title_sort hypoxic processes induce complement activation via classical pathway in porcine neuroretinas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700265/
https://www.ncbi.nlm.nih.gov/pubmed/34944083
http://dx.doi.org/10.3390/cells10123575
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