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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 1,1\u2032-dioctadecyl-3,3,3,3\u2032-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\u2013protein 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.<\/jats:p>","DOI":"10.3390\/genes12030403","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T20:17:40Z","timestamp":1615493860000},"page":"403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Retinal Genomic Fabric Remodeling after Optic Nerve Injury"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9459-3921","authenticated-orcid":false,"given":"Pedro Henrique","family":"Victorino","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Neurog\u00eanese, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Marra","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurog\u00eanese, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9700-6537","authenticated-orcid":false,"given":"Dumitru Andrei","family":"Iacobas","sequence":"additional","affiliation":[{"name":"Personalized Genomics Laboratory, Center for Computational Systems Biology, Prairie View A&amp;M University, Prairie View, TX 77446, USA"},{"name":"Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanda","family":"Iacobas","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Spray","sequence":"additional","affiliation":[{"name":"Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3287-336X","authenticated-orcid":false,"given":"Rafael","family":"Linden","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurog\u00eanese, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-9510","authenticated-orcid":false,"given":"Daniel","family":"Adesse","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilda","family":"Petrs-Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurog\u00eanese, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/bjo.86.2.238","article-title":"The definition and classification of glaucoma in prevalence surveys","volume":"86","author":"Foster","year":"2002","journal-title":"Br. 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