Novel Potential Drugs for Therapy of Age-Related Macular Degeneration Using Protein-Protein Interaction Network (PPI) Analysis

Abstract

Background: Age-related macular degeneration (AMD) is a common cause of blindness in older people. If diagnosed early, its progression in humans can be prevented.Material and Methods: To understand of AMD pathogenesis, this study was carried out to investigate differential gene expression in AMD and normal samples. Here, Differentially Expressed Genes (DEGs) with p-value of less than 0.01 were selected to construct the Protein- Protein interaction Network (PPI) using STRING web tool and visualized by Cytoscape software. Next, four PPI modules were discovered from the network. Then, the GO and pathway enrichment analyses were carried out on the modules’ genes. Drug- gene interactions were obtained for modules’ genes and reconstructed as a single drug- gene network.Results: Bevacisumab, Degzamethazone and Pegaptanib, as the most potent therapeutic candidatedrugs and previously mentioned as a therapy for AMD, had interaction with the genes associated with AMD. The other candidate drugs are Docetaxel, Cisplutin, Carboplatin, Methotrexate, Bexarotene, Raloxifene Hydrochloride, Acitretine, Adapalene, and Doxorubicine, some of which were previously discovered to be efficient against cancer. They had two gene targets in different modules.Conclusion: Computational tools are efficient for therapeutic goals, experimental validation of findings as well as testing of drug toxicity are critical for better treatment. Drugs proposed in this study might promote future studies on AMD.Keywords: Age-Related Macular Degeneration; Differential Gene Expression; Drug- Gene Network;Protein-Protein Interaction

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