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Integrated bioinformatic changes and analysis of retina with time in diabetic rats.

ABSTRACT: Diabetic retinopathy (DR) is the most common chronic complication of diabetes. It can cause impaired vision and even blindness. However, the pathological mechanism of DR is still unknown. In the present study, we use bioinformatic analysis to reveal the pathological changes of early DR in a streptozotocin (STZ) induced diabetes rat model. The dataset GSE28831 was downloaded from the Gene Expression Omnibus (GEO) database. To clarify the pathological mechanism of early DR, genes which were up-regulated (UP group) or down-regulated (DOWN group) over time were identified. One hundred eighty six genes in the UP group and 85 genes in the DOWN group were defined. There were in total 28 Gene ontology (GO) terms with a P value lower than 0.05 in UP group, including astrocyte development, neutrophil chemotaxis, neutrophil aggregation, mesenchymal cell proliferation and so on. In the DOWN group, there were totally 14 GO terms with a P value lower than 0.05, including visual perception, lens development in camera-type eye, camera-type eye development, bicellular tight junction and so on. Signaling pathways were analyzed with all genes in the UP and DOWN groups, and leukocyte transendothelial migration and tight junction were selected. Protein-protein interaction (PPI) network was constructed and six hub genes Diras3, Actn1, Tssk6, Cnot6l, Tek and Fgf4 were selected with connection degree ?5. S100a8, S100a9 and Tek may be potential targets for DR diagnosis and treatment. This study provides the basis for the diagnosis and treatment of DR in the future.

SUBMITTER: Cui Z

PROVIDER: S-EPMC5960260 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Integrated bioinformatic changes and analysis of retina with time in diabetic rats.

Cui Zekai Z Zeng Qiaolang Q Guo Yonglong Y Liu Shiwei S Chen Jiansu J

PeerJ 20180516

Diabetic retinopathy (DR) is the most common chronic complication of diabetes. It can cause impaired vision and even blindness. However, the pathological mechanism of DR is still unknown. In the present study, we use bioinformatic analysis to reveal the pathological changes of early DR in a streptozotocin (STZ) induced diabetes rat model. The dataset GSE28831 was downloaded from the Gene Expression Omnibus (GEO) database. To clarify the pathological mechanism of early DR, genes which were up-reg ...[more]

PMID: 29785346

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Project description:The aim of the present study was to investigate the changes in retinal gene expression at three time points and assess the underlying molecular mechanisms of diabetic retinopathy (DR) in a streptozotocin (STZ)-induced diabetes rat model using bioinformatics analysis. The gene expression profile of GSE28831 was extracted from the Gene Expression Omnibus database and differentially expressed genes (DEGs) were identified at three different time points (1, 4 and 12 weeks) using the limma package in R language. Gene ontology (GO) enrichment analysis of DEGs was performed followed by a principal component and pathway enrichment analysis of the selected DEGs along with protein-protein interaction network construction at the three time points. A total of 402, 105 and 213 DEGs were screened at 1, 4 and 12 weeks, respectively. In addition, the expression of 8 genes was identified to be significantly different at different time points, including cytochrome P450 2B2 (CYP2B2; downregulated gene; P=0.048; at 1 week), mannan binding lectin-associated serine protease-2 (MASP2; downregulated gene; P=0.044), lecithin retinol acyltransferase (LRAT; downregulated gene; P=0.015), retinal pigment epithelium (RPE)-specific protein 65 kDa (RPE65; downregulated gene; P=0.025), 11-cis-retinoldehydrogenase (RDH5; downregulated gene; P=0.04; at 4 weeks), mitogen-activated protein kinase 13 (MAPK13; upregulated gene; P=0.036), LRAT (downregulated gene; P=0.01) and RPE65 (downregulated gene; P=0.009; at 12 weeks). Furthermore, pathway enrichment and GO enrichment analyses revealed that DEGs at 4 weeks were primarily enriched in retinol metabolism and processes associated with visual functions, including 'visual perception' and 'retinol metabolism'. DEGs, including CYP2B2, MASP2, LRAT, RPE65, RDH5 and MAPK13 may be potential targets for the diagnosis and treatment of DR. Thus, the current study demonstrated that abnormal visual functions occur at 4 weeks in STZ-induced diabetic rats. This may provide a scientific basis for the diagnosis and treatment of DR because DEGs may be used to facilitate the development of novel therapeutic strategies to diagnose and treat DR.

Dataset Information

Integrated bioinformatic changes and analysis of retina with time in diabetic rats.

Publications

Integrated bioinformatic changes and analysis of retina with time in diabetic rats.

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