Comprehensive exploration of hub genes involved in oxidative stress in rhegmatogenous retinal detachment based on bioinformatics analysis

Abstract

Rhegmatogenous retinal detachment (RRD) is a type of ophthalmologic emergency, if left untreated, the blindness rate approaches 100 %. The RRD patient postoperative recovery of visual function is unsatisfactory, most notably due to photoreceptor death. We conducted to identify the key genes for oxidative stress (OS) in RRD through bioinformatics analysis and clinical validation, thus providing new ideas for the recovery of visual function in RRD patients after surgery. A gene database for RRD was obtained from the Gene Expression Omnibus (GEO) database (GSE28133). Then we screened differentially expressed OS genes (DEOSGs) from the database and assessed the critical pathways in RRD with Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Protein-protein interaction (PPI) networks and hub genes among the common DEOSGs were identified. In addition, we collected general information and vitreous fluid from 42 patients with RRD and 22 controls [11 each of epiretinal membrane (EM) and macular hole (MH)], examined the expression levels of proteins encoded by hub genes in vitreous fluid by enzyme-linked immunosorbent assay (ELISA) to further assess the relationship between the ELISA data and the clinical characteristics of patients with RRD. Ten hub genes (CCL2, ICAM1, STAT3, CD4, ITGAM, PTPRC, CCL5, IL18, TLR2, VCAM1) were finally screened out from the dataset. The ELISA results showed that, compared with the control group, patients with RRD: TLR2 and ICAM-1 were significantly elevated, and CCL2 had a tendency to be elevated, but no statistically significant; RRD patients and MH patients compared with EM patients: STAT3 and VCAM-1 were significantly elevated. We found affected eyes of RRD patients compared with healthy eyes: temporal and nasal retinal nerve fiber layer (RNFL) were significantly thickened. By correlation analysis, we found that: STAT3 was negatively correlated with ocular perfusion pressure (OPP); temporal RNFL was not only significantly positively correlated with CCL2, but also negatively correlated with Scotopic b-wave amplitude. These findings help us to further explore the mechanism of RRD development and provide new ideas for finding postoperative visual function recovery.

Keywords: Bioinformatics analysis; Biomarker; Hub gene; Oxidative stress; Rhegmatogenous retinal detachment.