RNA sequence analysis identified bone morphogenetic protein-2 (BMP2) as a biomarker underlying form deprivation myopia

Abstract

Purpose: Form deprivation myopia (FDM) is an urgent public issue characterized by pathological changes, but the underlying mechanism remained unclear. The aim was to investigate bone morphogenetic proteins (BMPs) utilizing the pathogenesis of FDM.

Material and methods: Gene expression omnibus (GEO) database was used to analyze one mRNA profile (GSE89325) of FDM. Sixteen retina samples (8 FDM and 8 controls) were randomly divided into seven groups for differential gene expression analysis in R. software. The gene pathway and protein-protein interaction (PPI) analysis were performed by the DAVID and STRING databases. Cytoscape was used to draw the PPI network. The gene ontology (GO) enrichment and Kyoto encyclopedia of genes and Genomes (KEGG) analysis were determined to achieve gene annotation and visualization.

Results: A total of 18420 differentially expressed genes (DEGs) were identified associated with FDM. The only non-significant gene (BEND6) was separately analyzed between two groups. Thirteen hub genes were discovered, ACVR1, ACVR2A, ACVR2B, RGMB, BMPR2, BMPR1A, BMP2, BMPR1B, CHRD, PTH, PTH1R, PTHLH, and WNT9A. The expression alteration in FDM were mainly enriched in cytokine-cytokine, and neuroactive ligand receptor interaction pathways. BMP2 was the key gene in myopia progression.

Conclusions: Of clinical perspective, our findings reveal that expression of BMP2 as an underlying mechanism of FDM, providing an insight for therapeutic interventions.

Keywords: Bone morphogenetic protein 2; Form deviation myopia; RNA sequence analysis; Retina.

Fig. 1

Plot of quality control for 15 SRR documents using multi-QC. Duplicate reads were identified using trim-gallore. QC, quality control.

Fig. 2

Differentially expressed genes and mRNAs in myopic retina. The volcano plot (a) showed that a total of 1 non-significant gene was detected to be differentially expressed. The heat map (b) detected that 16 mRNAs expressed differentially between myopic retina and controls, and 15 of them were upregulated.

Fig. 3

Differentially expressed genes in early and long term FDM retina. The volcano plot (a) showed that a total of 3 genes were detected to be differentially expressed between control and FDM 0 h; 2 were upregulated and 1 downregulated. The volcano plot (b) displayed that 13 genes expressed differentially between control and FDM 6 h, and 8 of them were upregulated. The volcano plot (c) displayed that 23 genes expressed differentially between control and FDM 24 h, and 7 of them were upregulated. In early FDM retina, 23 genes were differentially expressed in response to (FDM 0hrs vs FDM 6 h) (d), 26 genes in response to (FDM 0hrs vs FDM 24 h) (e), and 42 genes in response to (FDM 6hrs vs FDM 24 h) (f). Altogether, only WNT9A was downregulated in response to both FDM 0hrs vs FDM 6 h and FDM 0hrs vs FDM 24 h. FDM 0hrs: 0 h recovery from FD. FDM 6hrs: 6 h recovery from FD; FDM 24hrs: 24 h recovery from FD.

Fig. 4

Column plots showing all significant pathways from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway comparisons during the induction of myopia and recovery from FDM. The significantly enriched pathways are visualized for (a) 0 h versus 6 h, (b) 0 h versus 24 h, and (c) 0 h versus Control. The size of each column is proportional to the number of core genes within the pathway.

Fig. 5

Protein-protein interaction analysis of differentially expressed genes in response to control vs FDM 0hrs and bone morphogenetic protein 2 (BMP2) was identified as the key gene.