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Paul Wong, Deborah A. Ferrington, Timothy W. Olsen; Establishing a Human AMD Interactome. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6463.
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© ARVO (1962-2015); The Authors (2016-present)
Age related macular degeneration (AMD) is a leading cause of visual impairment in the developed world. AMD presents as a complicated progressive disorder involving multiple genetic and environmental factors. Understanding how proteins that are expressed over the course of AMD progression in the neurosensory macula (NSM) and the RPE are relevant to understanding the disease process. We took a meta-analysis approach at examining this issue.
Average protein or activity levels were mined from published studies examining AMD tissues graded using the Minnesota Grading system (MGS), which separates AMD tissue into 4 grades defining AMD grades 1 to 4. In total 32 abundant non-redundant AMD NSM expressed proteins and 29 AMD RPE expressed non-redundant proteins were ascertained. Proteins with significant fold changes were used to define each AMD transition stage (1: MGS 1-2; 2: MGS 2-3; 3: MGS 3-4). Protein lists were submitted to IPA analysis (Ingenuity Pathway Systems, Redwood City, CA) to define trends, biological pathways, and functional interactions over the course of AMD progression. Data retrieved from the informatic analyses were submitted to standard statistical analyses.
A single network interactome was established for both the AMD NSM and the AMD RPE list of proteins. Seven common proteins were found in both networks. In both cases a high number of proteins are involved with cell death and/or cell proliferation processes. Tests for homogeneity of biofunction terms demonstrated that the distribution of terms in NSM macula and RPE were independent of each other. Comparative analysis of proteins with significant fold differences at each AMD transition in a given tissue demonstrated that unique protein expression profiles define each AMD transition period.
The current networks generated provide a direct approach at illustrating how a diverse group of proteins that are expressed over AMD progression are functionally related. It illustrates at the molecular level how subtle alterations to the network might have an impact on the final phenotype. Finally it serves as a reference point from which additional proteins could be added to the network to refine our perspective of each AMD transition period over the course of disease progression.
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