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Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)

Ischemic retinal dystrophies are leading causes of acquired vision loss. Although the dysregulated expression of the hypoxia-responsive VEGF-A is a major driver of ischemic retinopathies, implication of additional VEGF-family members in their pathogenesis has led to the development of multivalent an...

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Autores principales: Rojo Arias, Jesús Eduardo, Jászai, József
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319207/
https://www.ncbi.nlm.nih.gov/pubmed/34321516
http://dx.doi.org/10.1038/s41598-021-94500-1
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author Rojo Arias, Jesús Eduardo
Jászai, József
author_facet Rojo Arias, Jesús Eduardo
Jászai, József
author_sort Rojo Arias, Jesús Eduardo
collection PubMed
description Ischemic retinal dystrophies are leading causes of acquired vision loss. Although the dysregulated expression of the hypoxia-responsive VEGF-A is a major driver of ischemic retinopathies, implication of additional VEGF-family members in their pathogenesis has led to the development of multivalent anti-angiogenic tools. Designed as a decoy receptor for all ligands of VEGFR1 and VEGFR2, Aflibercept is a potent anti-angiogenic agent. Notwithstanding, the molecular mechanisms mediating Aflibercept’s efficacy remain only partially understood. Here, we used the oxygen-induced retinopathy (OIR) mouse as a model system of pathological retinal vascularization to investigate the transcriptional response of the murine retina to hypoxia and of the OIR retina to Aflibercept. While OIR severely impaired transcriptional changes normally ensuing during retinal development, analysis of gene expression patterns hinted at alterations in leukocyte recruitment during the recovery phase of the OIR protocol. Moreover, the levels of Angiopoietin-2, a major player in the progression of diabetic retinopathy, were elevated in OIR tissues and consistently downregulated by Aflibercept. Notably, GO term, KEGG pathway enrichment, and expression dynamics analyses revealed that, beyond regulating angiogenic processes, Aflibercept also modulated inflammation and supported synaptic transmission. Altogether, our findings delineate novel mechanisms potentially underlying Aflibercept’s efficacy against ischemic retinopathies.
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spelling pubmed-83192072021-07-29 Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap) Rojo Arias, Jesús Eduardo Jászai, József Sci Rep Article Ischemic retinal dystrophies are leading causes of acquired vision loss. Although the dysregulated expression of the hypoxia-responsive VEGF-A is a major driver of ischemic retinopathies, implication of additional VEGF-family members in their pathogenesis has led to the development of multivalent anti-angiogenic tools. Designed as a decoy receptor for all ligands of VEGFR1 and VEGFR2, Aflibercept is a potent anti-angiogenic agent. Notwithstanding, the molecular mechanisms mediating Aflibercept’s efficacy remain only partially understood. Here, we used the oxygen-induced retinopathy (OIR) mouse as a model system of pathological retinal vascularization to investigate the transcriptional response of the murine retina to hypoxia and of the OIR retina to Aflibercept. While OIR severely impaired transcriptional changes normally ensuing during retinal development, analysis of gene expression patterns hinted at alterations in leukocyte recruitment during the recovery phase of the OIR protocol. Moreover, the levels of Angiopoietin-2, a major player in the progression of diabetic retinopathy, were elevated in OIR tissues and consistently downregulated by Aflibercept. Notably, GO term, KEGG pathway enrichment, and expression dynamics analyses revealed that, beyond regulating angiogenic processes, Aflibercept also modulated inflammation and supported synaptic transmission. Altogether, our findings delineate novel mechanisms potentially underlying Aflibercept’s efficacy against ischemic retinopathies. Nature Publishing Group UK 2021-07-28 /pmc/articles/PMC8319207/ /pubmed/34321516 http://dx.doi.org/10.1038/s41598-021-94500-1 Text en © The Author(s) 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 Article
Rojo Arias, Jesús Eduardo
Jászai, József
Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)
title Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)
title_full Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)
title_fullStr Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)
title_full_unstemmed Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)
title_short Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)
title_sort gene expression profile of the murine ischemic retina and its response to aflibercept (vegf-trap)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319207/
https://www.ncbi.nlm.nih.gov/pubmed/34321516
http://dx.doi.org/10.1038/s41598-021-94500-1
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