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

Abstract 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 multi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jesús Eduardo Rojo Arias, József Jászai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6774ec12cbe6423b8646f647eb2f6254
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6774ec12cbe6423b8646f647eb2f6254
record_format	dspace
spelling	oai:doaj.org-article:6774ec12cbe6423b8646f647eb2f62542021-12-02T16:31:48ZGene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)10.1038/s41598-021-94500-12045-2322https://doaj.org/article/6774ec12cbe6423b8646f647eb2f62542021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94500-1https://doaj.org/toc/2045-2322Abstract 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.Jesús Eduardo Rojo AriasJózsef JászaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jesús Eduardo Rojo Arias József Jászai Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap)
description	Abstract 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.
format	article
author	Jesús Eduardo Rojo Arias József Jászai
author_facet	Jesús Eduardo Rojo Arias József Jászai
author_sort	Jesús Eduardo Rojo Arias
title	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_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_sort	gene expression profile of the murine ischemic retina and its response to aflibercept (vegf-trap)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6774ec12cbe6423b8646f647eb2f6254
work_keys_str_mv	AT jesuseduardorojoarias geneexpressionprofileofthemurineischemicretinaanditsresponsetoafliberceptvegftrap AT jozsefjaszai geneexpressionprofileofthemurineischemicretinaanditsresponsetoafliberceptvegftrap
_version_	1718383877544738816

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

Ejemplares similares