Effect of intravitreal conbercept treatment on the expression of Long Noncoding RNAs and mRNAs in Proliferative Diabetic Retinopathy Patients

Purpose: To evaluate the effect of conbercept on the expression of long noncoding RNAs (lncRNAs) and mRNAs in the fibrovascular membranes of proliferative diabetic retinopathy (PDR) patients.

Methods: Twenty patients, diagnosed with PDR, who underwent pars plana vitrectomy (PPV), were recruited for this study. Ten patients were treated for PPV alone (Control Group), and the others received conbercept injections before PPV (Treated Group). The fibrovascular membranes were harvested during surgery. Expression of lncRNAs and mRNAs in the membranes was tested using lncRNA Arrays. Bioinformatics analyses were performed to identify the related biological modules and pathways of the differentially expressed genes. A lncRNA/mRNA coexpression network was built to identify the correlations between lncRNAs and mRNAs. Real-time PCR was conducted to verify the microarray results.

Results: We identified 427 differentially expressed lncRNAs, of which 263 were upregulated and 164 were downregulated. Gene ontology (GO) analysis indicated that these lncRNAs-coexpressed mRNAs targeted various metabolic processes, especially the gluconeogenesis. Kyoto Encyclopaedia of Genes and Genomes (KEGG) results indicated that 16 pathways had significant differences in gene expression, including gluconeogenesis, HIF-1 signalling pathway, NOD-like receptor pathway, etc. The lncRNA/mRNA coexpression network revealed that many differentially expressed lncRNAs were enriched in the HIF-1, TNF-α and NOD-like receptor pathways. LincRNAs were the largest category and further bioinformatics analysis implied that these lincRNAs-coexpressed mRNAs were mainly involved in PDR-related biological processes and pathological pathways.

Conclusion: Conbercept treatment can change the expression profiles of lncRNAs and mRNAs in the fibrovascular membranes of PDR patients. A complete understanding of the relationship between lncRNAs and anti-VEGF drugs may contribute to new therapeutic regimen for PDR.