Transcriptome-wide analysis of the CXCR5-defcicient retinal pigment epithelial cells (RPE) reveals novel molecular mechanisms of RPE cell homeostasis

Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in the elderly. Our previous studies found that CXCR5 deficiency causes AMD-like pathological phenotypes in mice, which are associated with abnormalities and dysfunction of the retinal pigment epithelium (RPE) cells. The objective of the present study is to perform a genome-wide transcriptomic analysis of the normal RPE cells and the RPE cells with CXCR5 deficiency. The primary RPE cells derived from the CXCR5 knockout (KO) mice and C57BL6 wild type (WT) mice were cultured, and the RNAs were isolated from library preparation, sequenced and sequencing data analyzed. Principle component analysis (PCA), hierarchic clustering and Pearson coefficient analyses of gene expression levels indicated that differences between two groups. A total of 1392 (693 up-regulated and 699 down-regulated genes) differentially expressed genes (DEG) were identified. Function gene ontology analyses showed various biological process, cellular component and molecular functions. Function pathway enrichment and gene-gene network disclosed the PI3K-Akt signaling pathway, mTOR signaling pathway, FOXO pathway, Focal adhesion, Endocytosis, Ubiquitin mediated proteolysis, TNF-alpha NF-kB Signaling Pathway, Adipogenesis genes, p53 signaling, Ras Pathway, autophagy, Epithelial-Mesenchymal Transition (EMT) and mitochondrial pathway genes were most enriched. The outcomes explore the new molecular signaling of CXCR5 gene deficiency.