Abstract
BackgroundThe aim of this research was to investigate the retinal transcriptome changes in long‐term streptozotocin (STZ)‐induced rats' retinas using RNA sequencing (RNA‐seq), to explore the molecular mechanisms of diabetic retinopathy (DR), and to identify novel targets for the treatment of DR by comparing the gene expression profile we obtained.MethodsIn this study, 6 healthy male SD rats were randomly divided into wild‐type (WT) group and streptozotocin (STZ)‐induced group, 3 rats each group. After 6 months, 3 normal retina samples and 3 DM retina samples (2 retinas from the same rat were considered as 1 sample) were tested and differentially expressed genes (DEGs) were measured by RNA‐seq technology. Then, we did Gene Ontology (GO) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and validated the results of RNA‐seq through qRT–PCR.ResultsA total of 118 DEGs were identified, of which 72 were up‐regulated and 46 were down‐regulated. The enriched GO terms showed that 3 most significant enrichment terms were binding (molecular function), cell part (cellular component), and biological regulation (biological process). The results of the KEGG pathway analysis revealed a significant enrichment in cell adhesion molecules, PI3K‐Akt signaling pathway, and allograft rejection, etc.ConclusionOur research has identified specific DEGs and also speculated their potential functions, which will provide novel targets to explore the molecular mechanisms of DR.
Highlights
With the notably increasing population of diabetes, diabetic retinopathy (DR), one of the most severe complications of diabetes, has the potential to be the leading cause of blindness worldwide (Klein, 2007; Yau et al, 2012)
These pathways can cause up-regulation of factors such as insulin-like growth factor (IGF, OMIM: 147440), vascular endothelial growth factor (VEGF, OMIM: 192240), tumor necrosis factor (TNF, OMIM: 191160), and basic fibroblast growth factor-2 that can promote the occurrence of DR (Safi, Qvist, & Kumar, 2014)
Compared with the results of transcriptomic analysis which use CD31+ vascular endothelial cells obtained from human PDR fibrovascular membranes (FVM) (Lam et al, 2017), we found the gene Col3a1 were both significantly changed, and according to the Gene Ontology (GO) enrichment analysis of two researches, Col3a1 may belong to blood vessel development term (GO:0001568), suggested that Col3a1 may play a role in DR neovascularization
Summary
This study was supported by The National Key R&D Program of China (Grant No: 2016YFC0904800), The National Natural Science Foundation (Grant No: 81870667), and The Scientific research project of Shanghai Science and Technology Commission (Grant No: 17140903200).
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