No abstract

Both HIF-1α and Robo4 may have a vital role during the formation of FVM. The increased or decreased expression of Robo4 by stimulation or knockdown of HIF-1α suggesting that Robo4 is positively regulated by HIF-1α under normoxic and hypoxic conditions in microvascular endothelial cells in vitro. The HIF-1α gene promotes HREC invasion and proliferation by transcriptionally upregulating Robo4 under hypoxic conditions.

Knockdown of Robo4 expression in HRVECs induced endothelial hyperpermeability associated with the downregulation of ZO-1, occludin, and the rearrangement of F-actin and that LIM-kinase 1 (LIMK1)/cofilin signal transduction system may be involved in the modulating process.

Background: Diabetic retinopathy (DR) is a serious complication of diabetes that can lead to blindness. This study aimed to identify the core genes and molecular functions involved in DR through multiple bioinformatics analyses. Material/Methods: The mRNA gene profiles of human DR tissues from the GSE60436 and GSE53257 datasets were assessed with R software and integrated to identify the co-expressed differentially expressed genes (DEGs). Multiple bioinformatics analyses were used: Gene Ontology (GO) analysis, signaling pathway analysis, and hub gene prediction. Quantitative reverse transcription-PCR (qRT-PCR) was used to verify the hub genes. Results: The Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool suggested that the biological processes of the DEGs focused on mitochondrial transport, the cellular components focused on mitochondria, and molecular functions focused on catalytic activity. The results provided by DAVID were consistent with those provided by STRING and the GeneMANIA online database. All the DEGs function in metabolic pathways, consistent with the g: Profiler online analysis results. The protein-protein interaction (PPI) networks forecasted by STRING and GeneMANIA were entered into Cytoscape for cytoHubba degree analysis. The hub genes predicted by cytoHubba suggested that fumarate hydratase (FH) might be relevant to DR. qRT-PCR suggested that the expression of FH was higher in DR retinal tissues than in normal control tissues. Conclusions: Multiple bioinformatics analyses verified that FH could be used as a potential diagnostic marker and new therapeutic target of DR.

Diabetic retinopathy (DR) is a significant complication of diabetes. During the pathogenesis of retinal microangiopathy and neuronopathy, activated retinal Müller cells (RMCs) undergo morphological and structural changes such as increased expression of glial fibrillary acidic protein, disturbance of potassium and water transport regulation, and onset of production of a large number of inflammatory and vascular growth factors as well as chemokines. Evidently, activated RMCs are necessary for the pathogenesis of DR; therefore, exploring the role of RMCs in DR may provide a new target for the treatment thereof. This article reviews the mechanism of RMCs involvement in DR and the progress in related treatments.