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Data · dataset · 2018

Identification of functional networks associated with cell death in the retina of OXYS rats during the development of retinopathy

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Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the molecular pathogenesis of early events in AMD is poorly understood.

Description

Senescence-accelerated OXYS rats develop AMD-like retinopathy. The aim of this study was to explore the differences in retinal gene expression between OXYS and Wistar (control) rats at age 20 d and to identify the pathways of retinal cell death involved in the OXYS retinopathy initiation and progression.

Retinal mRNA profiles of 20-day-old OXYS and Wistar rats were generated at the sequencing read depth 40 mln, in triplicate, using Illumina GAIIx. A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay was performed to measure the apoptosis level. GeneMANIA was used to construct interaction networks for differentially expressed (DE) apoptosis-related genes at ages 20 d and 3 and 18 months.

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Functional analysis was suggestive of a developmental process, signal transduction, and cell differentiation as the most enriched biological processes among 245 DE genes at age 20 d An increased level of apoptosis was observed in OXYS rats at age 20 d but not at advanced stages. We identified functional clusters in the constructed interaction networks and possible hub genes ( Rasa1, cFLAR, Birc3, Cdk1, Hspa1b, Erbb3 , and Ntf3) .

We also demonstrated the significance of the extrinsic apoptotic pathway at preclinical, early, and advanced stages of retinopathy development. Besides the cell death signaling pathways, immune system-related processes and lipid-metabolic processes showed overrepresentation in the clusters of all networks. These characteristics of the expression profile of the genes functionally associated with apoptosis may contribute to the pathogenesis of AMD-like retinopathy in senescence-accelerated OXYS rats.

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Cancer · Medicine & Health
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Sequencing 75%
Provenance · 1 source records, 14 field assertions
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DataCite10.6084/m9.figshare.156899111 d agoJSON v1
FieldAssertionExtractorEvidence
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