Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Optic Nerve Crush Activates the Genomic Fabrics of the Complement Cascade and Delta-Notch Signaling

Pedro Henrique Victorino
ORCID logo ,
Camila Marra
,
Dumitru Andrei Iacobas
ORCID logo ,
Sanda Iacobas
,
David C Spray
,
Rafael Linden
ORCID logo ,
Daniel Adesse
* ORCID logo ,
Hilda Petrs-Silva
*
Version 1 : Received: 31 March 2020 / Approved: 2 April 2020 / Online: 2 April 2020 (11:59:28 CEST)
Version 2 : Received: 19 February 2021 / Approved: 23 February 2021 / Online: 23 February 2021 (12:44:20 CET)

How to cite: Victorino, P.H.; Marra, C.; Iacobas, D.A.; Iacobas, S.; Spray, D.C.; Linden, R.; Adesse, D.; Petrs-Silva, H. Optic Nerve Crush Activates the Genomic Fabrics of the Complement Cascade and Delta-Notch Signaling. Preprints 2020, 2020040016. https://doi.org/10.20944/preprints202004.0016.v1 Victorino, P.H.; Marra, C.; Iacobas, D.A.; Iacobas, S.; Spray, D.C.; Linden, R.; Adesse, D.; Petrs-Silva, H. Optic Nerve Crush Activates the Genomic Fabrics of the Complement Cascade and Delta-Notch Signaling. Preprints 2020, 2020040016. https://doi.org/10.20944/preprints202004.0016.v1

Abstract

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 applied systems biology approaches to better understand the molecular mechanisms related with the retinal remodeling after induction of RGC degeneration. 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. Enrichment analysis showed that Complement cascade and Notch signaling pathway were the main affected pathways after ONC. To expand our studies of these two pathways, we examined the coordination of gene expressions within each pathway and with the entire transcriptome. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles. This study provided novel findings beyond the regulation of individual gene expression and disclosed changes in the control of expression by Complement cascade and Notch signaling functional pathways important for both RGC degeneration and remodeling of the retinal tissue after ONC.

Keywords

glaucoma; retina ganglion cell degeneration; microarray; genes coordination; notch signaling pathway; complement cascade

Subject

Biology and Life Sciences, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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