Exploring the potential mechanism and screening small molecule drugs for glaucoma by using bioinformatics approach

Q. Liao, X.-Y. Sun, H. Guo, C. Li

Department of Ophthalmology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. guohonggh123@gmail.com

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• Ophthalmology

BACKGROUND: Glaucoma is a neurodegenerative disease which is the second most common cause of blindness worldwide.

AIM: To investigate the mechanism of glaucoma and identify small molecule drugs.

MATERIALS AND METHODS: Gene expression profiles of GSE2378 were downloaded from Gene Expression Omnibus (GEO) database which included 15 astrocytes from 8 and 7 donors with and without glaucoma, respectively. Then the raw data were normalized by Robust Multichip Averaging and the differentially expressed genes (DEGs) were identified with limma package in R. Moreover, the Gene Ontology and pathway enrichment analyses were performed by GOEAST and Gene Set Analysis Toolkit V2, respectively. In addition, the potential target sites of transcription factors were detected using MSigDB. Finally, small molecule drugs were screened for glaucoma treatment by Connectivity Map.

RESULTS: A total of 961 DEGs between glaucoma and normal cells were identified. These DEGs were discovered mainly involved in cell surface, molecule binding, changes in protein activity and signal transduction. Additionally, the most significant pathway was pathway in cancer (FDR = 0.0051). Some DEGs shared target sites of the transcription factor, such as NFκB. (FDR = 0.0132) and PBX1 (FDR = 0.0158). Luteolin (enrichment = 0.87) can simulate the state of normal cells, while vancomycin (enrichment = -0.883) and Prestwick-1082 (enrichment = -0.882) might be potential pathogenic substances.

CONCLUSIONS: We hypothesize that glaucoma cells may be not only caused by the optic nerve cells themselves, but also caused by infections due to resistance decline. All these results may facilitate glaucoma treatment with a new breakthrough.

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