Purpose: Retinal pigment epithelial cell autophagy dysfunction, cellular senescence, and the retinal inflammatory response are key pathogenic factors in age-related macular degeneration (AMD), which has been reviewed in our previously work in 2019. This study aims to identify genes collectively involved in these three biological processes and target drugs in AMD.
Methods: The pubmed2ensembl database was used to perform text mining. The GeneCodis database was applied to analyze gene ontology biological process and the KEGG pathway. The STRING database was used to analyze protein-protein interaction analysis and hub genes were identified by the Cytoscape software. The Drug Gene Interaction Database was used to perform drug-gene interactions.
Results: We identified 62 genes collectively involved in AMD, autophagy, cellular senescence, and inflammatory response, 19 biological processes including 42 genes, 11 enriched KEGG pathways including 37 genes, and 12 hub genes step by step via the above biomedical databases. Finally, five hub genes (IL-6, VEGF-A, TP53, IL-1β, and transforming growth factor [TGF]-β1) and their specific interaction modes were identified, corresponding with 24 target drugs with therapeutic potential for AMD.
Conclusions: IL-6, VEGF-A, TP53, IL-1β, and TGF-β1 are pivotal in autophagy, cellular senescence, and the inflammatory response in AMD, corresponding with 24 drugs with therapeutic potential for AMD, providing definite molecular mechanisms for further research and new possibilities for AMD treatment in the future.
Translational relevance: IL-6, VEGF-A, TP53, IL-1β, and TGF-β1 may be new targets for AMD gene therapy and drug development.
Keywords: age-related macular degeneration; autophagy; cellular senescence; common genes; drugs; inflammatory response.
Copyright 2021 The Authors.