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Johannes Schouten, Ilona Liesenborghs, Lars Eijssen, Martina Kutmon, Theo G M F Gorgels, Chris Evelo, Henny J Beckers, Carroll Webers; Molecular pathway analyses with bioinformatics in trabecular meshwork cells of patients with primary open angle glaucoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5625.
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© ARVO (1962-2015); The Authors (2016-present)
The pathogenesis of primary open angle glaucoma (POAG) has not been clarified and its treatment is not based on insights in the molecular mechanisms. We performed in silico pathway and network analysis in gene expression datasets of trabecular meshwork cells in patients with and without POAG. This contributes to a better insight in the molecular mechanisms in POAG and may provide new treatment options.
We analysed a microarray dataset (GSE27276; 15 cases and 13 controls) in which the gene expression profiles of patients with and without POAG are compared. A search for these datasets was conducted in Gene Expression Omnibus. The data were subjected to a thorough quality control based on ArrayAnalysis.org and R scripts. Divergent data were removed from further analysis. Pathway analysis and visualisation was conducted with PathVisio. Pathways from WikiPathways were used. Pathways with Z-score > 1.96, permuted p-value < 0.05, and ≥ 3 changed genes were considered significantly changed. In Cytoscape, the identified pathways were combined into a network of interacting genes.
One of the patients had a MYOC-mutation and appeared as an outlier in the quality control. Therefore, this sample was removed for further analysis. Pathway analysis showed 16 significantly altered pathways. Some of these pathways are already associated with glaucoma: the complement activation pathway (WP545), the focal adhesion pathway (WP306), the miRNA targets in ECM and membrane receptors pathway (WP2911), and the regulation of actin cytoskeleton pathway (WP51). For example, in the complement activation pathway, in particular the classical pathway, the genes are upregulated, indicating activation. Studies in other tissues revealed that not only known immunoglobulins but also multiple other triggers are able to activate this pathway. Further research on this and the other identified pathways may identify new insights in the molecular mechanisms of POAG. Also, further visualising these pathways into a network of interacting genes may help to identify candidate genes and treatment options.
We identified 16 pathways that seem to play a role in POAG. Molecular pathway and network analysis with bioinformatics can give us new insights into the molecular mechanisms of primary open angle glaucoma.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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