Retinal Genomic Fabric Remodeling after Optic Nerve Injury

Detalhes bibliográficos
Autor(a) principal: Victorino, Pedro Henrique
Data de Publicação: 2021
Outros Autores: Marra, Camila, Iacobas, Dumitru Andrei, Iacobas, Sandra, Spray, David C., Linden, Rafael, Adesse, Daniel, Petrs-Silva, Hida
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/48141
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neurogênese. Rio de Janeiro, RJ, Brasil.
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spelling Victorino, Pedro HenriqueMarra, CamilaIacobas, Dumitru AndreiIacobas, SandraSpray, David C.Linden, RafaelAdesse, DanielPetrs-Silva, Hida2021-07-12T13:10:14Z2021-07-12T13:10:14Z2021VICTORINO, Pedro Henrique et al. Retinal Genomic Fabric Remodeling after Optic Nerve Injury. Genes, v. 12, n. 3, 25 p, Mar. 2021.2073-4425https://www.arca.fiocruz.br/handle/icict/4814110.3390/genes12030403engMDPIGlaucomaDegeneração celular gânglio da retinaCoordenação de genesCaminho de sinalização de entalheCascata complementarMicro arranjosGlaucomaRetinal ganglion cell degenerationMicroarrayGenes coordinationNotch signaling pathwayComplement cascadeRetinal Genomic Fabric Remodeling after Optic Nerve Injuryinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neurogênese. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neurogênese. Rio de Janeiro, RJ, Brasil.Personalized Genomics Laboratory, Center for Computational Systems Biology, Prairie View A&M University. Prairie View, TX 77446, USA / Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.Department of Pathology, New York Medical College, Valhalla, NY 10595, USA.Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neurogênese. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neurogênese. Rio de Janeiro, RJ, Brasil.Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the genomic fabric paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers three independent characteristics for the expression of each gene: level, variability, and correlation with each other gene. Thus, the 17,657 quantified genes in our study generated a total of 155,911,310 values to analyze. This represents 8830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with 1,10 -dioctadecyl-3,3,3,30 -tetramethylindocarbocyanine perchlorate (DiI). We observed a higher relative expression variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted protein–protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among upregulated genes. Enrichment analysis showed that complement cascade and Notch signaling pathway, as well as oxidative stress and kit receptor pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pairwise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in complement cascade and Notch signaling pathway. This deep bioinformatic study provided novel insights beyond the regulation of individual gene expression and disclosed changes in the control of expression of complement cascade and Notch signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/48141/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALDaniel_Adesse_etal_IOC_2021.pdfDaniel_Adesse_etal_IOC_2021.pdfapplication/pdf5342084https://www.arca.fiocruz.br/bitstream/icict/48141/2/Daniel_Adesse_etal_IOC_2021.pdf8b6dabec43078c2fd941f9f344fd5f66MD52TEXTDaniel_Adesse_etal_IOC_2021.pdf.txtDaniel_Adesse_etal_IOC_2021.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Retinal Genomic Fabric Remodeling after Optic Nerve Injury
title Retinal Genomic Fabric Remodeling after Optic Nerve Injury
spellingShingle Retinal Genomic Fabric Remodeling after Optic Nerve Injury
Victorino, Pedro Henrique
Glaucoma
Degeneração celular gânglio da retina
Coordenação de genes
Caminho de sinalização de entalhe
Cascata complementar
Micro arranjos
Glaucoma
Retinal ganglion cell degeneration
Microarray
Genes coordination
Notch signaling pathway
Complement cascade
title_short Retinal Genomic Fabric Remodeling after Optic Nerve Injury
title_full Retinal Genomic Fabric Remodeling after Optic Nerve Injury
title_fullStr Retinal Genomic Fabric Remodeling after Optic Nerve Injury
title_full_unstemmed Retinal Genomic Fabric Remodeling after Optic Nerve Injury
title_sort Retinal Genomic Fabric Remodeling after Optic Nerve Injury
author Victorino, Pedro Henrique
author_facet Victorino, Pedro Henrique
Marra, Camila
Iacobas, Dumitru Andrei
Iacobas, Sandra
Spray, David C.
Linden, Rafael
Adesse, Daniel
Petrs-Silva, Hida
author_role author
author2 Marra, Camila
Iacobas, Dumitru Andrei
Iacobas, Sandra
Spray, David C.
Linden, Rafael
Adesse, Daniel
Petrs-Silva, Hida
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Victorino, Pedro Henrique
Marra, Camila
Iacobas, Dumitru Andrei
Iacobas, Sandra
Spray, David C.
Linden, Rafael
Adesse, Daniel
Petrs-Silva, Hida
dc.subject.other.pt_BR.fl_str_mv Glaucoma
Degeneração celular gânglio da retina
Coordenação de genes
Caminho de sinalização de entalhe
Cascata complementar
Micro arranjos
topic Glaucoma
Degeneração celular gânglio da retina
Coordenação de genes
Caminho de sinalização de entalhe
Cascata complementar
Micro arranjos
Glaucoma
Retinal ganglion cell degeneration
Microarray
Genes coordination
Notch signaling pathway
Complement cascade
dc.subject.en.pt_BR.fl_str_mv Glaucoma
Retinal ganglion cell degeneration
Microarray
Genes coordination
Notch signaling pathway
Complement cascade
description Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neurogênese. Rio de Janeiro, RJ, Brasil.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-07-12T13:10:14Z
dc.date.available.fl_str_mv 2021-07-12T13:10:14Z
dc.date.issued.fl_str_mv 2021
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv VICTORINO, Pedro Henrique et al. Retinal Genomic Fabric Remodeling after Optic Nerve Injury. Genes, v. 12, n. 3, 25 p, Mar. 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/48141
dc.identifier.issn.pt_BR.fl_str_mv 2073-4425
dc.identifier.doi.none.fl_str_mv 10.3390/genes12030403
identifier_str_mv VICTORINO, Pedro Henrique et al. Retinal Genomic Fabric Remodeling after Optic Nerve Injury. Genes, v. 12, n. 3, 25 p, Mar. 2021.
2073-4425
10.3390/genes12030403
url https://www.arca.fiocruz.br/handle/icict/48141
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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