A systems genetics approach to revealing the molecular network of the retina.

Purpose: Platelet-derived growth factor (PDGF) signaling is well known to be involved in vascular retinopathies. Among the PDGF family, the subunit B (PDGFB) protein is considered a promising therapeutic target. This study aimed to identify the genes and potential pathways through which PDGFB affects retinal phenotypes by using a systems genetics approach.

Methods: Gene expression data had been previously generated in a laboratory for the retinas of 75 C57BL/6J(B6) X DBA/2J (BXD) recombinant inbred (RI) strains. Using this data, the genetic correlation method was used to identify genes correlated to . A correlation between intraocular pressure (IOP) and was calculated based on the Pearson correlation coefficient. A gene set enrichment analysis and the STRING database were used to evaluate gene function and to construct protein-protein interaction (PPI) networks.

Results: was a -regulated gene in the retina; its expression had a significant correlation with IOP (r = 0.305; p value = 0.012). The expression levels of 2,477 genes also had significant correlations with expressions (p<0.05), among which was the most positively correlated (r = 0.628; p value = 1.29e-10). Thus, was highly expressed in the retina and shared the transcription factor (TF) binding site with . Gene Ontology and a pathway analysis revealed that  and its covariates were highly involved in mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor (VEGF) pathways. A generated gene network indicated that  was directly connected to and interacted with other genes with similar biologic functions.

Conclusions: A systems genetics analysis revealed that  had significant interactions with and other genes in MAPK and VEGF pathways, through which was important in maintaining retina function. These findings provided basic information regarding the regulation mechanism and potential therapy for vascular retinopathies.