Genome-Wide Expression Profiling of Patients with Primary Open Angle Glaucoma

PURPOSE. To identify differentially expressed genes and to elucidate gene interaction networks and molecular pathways possibly contributing to the development of POAG. METHODS. Genome-wide expression profiling experiments were carried out using ABI high-density oligonucleotide microarrays in leukocytes from 25 POAG patients and 12 age-, ethnicity-, and sex-matched normal controls. Significantly modulated genes were defined as those with a false discovery rate (FDR) < 0.01 and an absolute fold change (FC) > 1.5. These genes are then mapped to relevant biologic processes and pathways. RESULTS. We identified 563 genes that were significantly dysregulated (410 upregulated and 153 downregulated) in POAG compared with normal controls ("POAG gene signature"). These genes were significantly enriched with functions related to, among others, nucleoside, nucleotide, and nucleic acid metabolism, the mitogen-activated protein kinase kinase kinase cascade, apoptosis, protein synthesis, cell cycle, intracellular signaling cascade, and nervous system development and function. Among the most significantly altered canonical pathways in POAG were the ephrin receptor signaling, ubiquitin proteasome pathway, hypoxia signaling, neuregulin, and G-protein coupled receptor signaling. Network analysis revealed potentially critical roles of UBE2, TBP, GNAQ, SUMO1, CREB, p70S6k, IFNG, and CaMKII that are interacting with NF-kappa B, ubiquitin, proteasome, PI3K/AKT, IL12, and PDGF in the disease pathogenesis. CONCLUSIONS. Our study revealed blood gene signatures that clearly distinguish POAG patients and normal controls, as well as altered pathways that may shed light on POAG pathogenesis. (Invest Ophthalmol Vis Sci. 2012; 53:5899-5904) DOI: 10.1167/iovs.12-9634