期刊
NPJ AGING AND MECHANISMS OF DISEASE
卷 6, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41514-019-0039-5
关键词
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资金
- European Union's Horizon 2020 research and innovation program [634479]
- National Institute for Health Research (NIHR) Biomedical Research Center at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London
- Spanish Ministry of Economy and Competitiveness [BIO2012-39754]
- European Fund for Regional Development
- Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013-2017 [SEV-2012-0208]
Age-related macular degeneration (AMD) is one of the commonest causes of sight loss in the elderly population and to date there is no intervention that slows or prevents early AMD disease progressing to blinding neovascularization or geographic atrophy. AMD is a complex disease and factors proposed to contribute to the development and progression of disease include aging, genetics, epigenetics, oxidative stress, pro-inflammatory state, and life-style factors such as smoking, alcohol, and high fat diet. Here, we generate a knowledge repository of pathways and protein-protein interaction (PPI) networks likely to be implicated in AMD pathogenesis, such as complement activation, lipid trafficking and metabolism, vitamin A cycle, oxidative stress, proteostasis, bioenergetics, autophagy/mitophagy, extracellular matrix (ECM) turnover, and choroidal vascular dropout. Two disctinct clusters ermerged from the networks for parainflamation and ECM homeostasis, which may represent two different disease modules underlying AMD pathology. Our analyses also suggest that the disease manifests primarily in RPE/choroid and less in neural retina. The use of standardized syntax when generating maps of these biological processes (SBGN standard) and networks (PSI standard) enables visualization of complex information in graphical programs such as CellDesigner and Cytoscape and enhances reusability and extension of data. The ability to focus onto subnetworks, multiple visualizations and simulation options will enable the AMD research community to computationally model subnetworks or to test experimentally new hypotheses arising from connectivities in the AMD pathway map.
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