June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Is AMD a Disease or a Disorder? A Systems Biology Attempt to Subtype AMD on the Basis of Gene Expression
Author Affiliations & Notes
  • Mones Abu-Asab
    Histopathology Core, National Eye Institute, Bethesda, MD
  • Chi-Chao Chan
    Histopathology Core, National Eye Institute, Bethesda, MD
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • Footnotes
    Commercial Relationships Mones Abu-Asab, None; Chi-Chao Chan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6165. doi:https://doi.org/
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      Mones Abu-Asab, Chi-Chao Chan; Is AMD a Disease or a Disorder? A Systems Biology Attempt to Subtype AMD on the Basis of Gene Expression. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6165. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Genetic pathways underlying the initiation and progression of age-related macular degeneration (AMD) have not been yet sufficiently revealed, and whether AMD’s phenotypes represent a single disease or a disorder with an assemblage of diseases is still awaiting resolution. We attempt to tackle both problems with a systems biology analytical paradigm called parsimony phylogenetics.


We profiled genome wide gene expression data of macular and extra-macular specimens of retinas (55 normal, 13 pre-AMD, and 47 AMD) and retinal pigment epithelium (RPE)-choroids (96 normal, 21 pre-AMD, and 60 AMD). The AMD specimens encompassed dry-AMD without geographic atrophy (GA), choroidal neovascularization (CNV), and GA (GEO DataSets: GSE29801). Pre-AMD and AMD gene expression values of retinal and RPE-choroidal specimens were polarized separately against their respective normal specimens, and the new polarized data matrices were processed through MIX, a parsimony program of the PHYLIP package, to produce phylogenetic cladograms for both sets of data. Gene lists extracted from the cladograms nodes were processed in Genomatix GePS to generate pathway networks.


Cladograms indicated heterogeneous gene-expression profiles within phenotypic subtypes commonly classified with conventional diagnostic systems. AMD phenotypes were not distinct according to their transcriptome profiles of the retina or RPE-Choroid suggesting more clinical subtypes than those currently recognized. Macular and temporal extra-macular tissues of the same patient separated in most of the retinal and RPE sets but some clustered together.


The topology, groupings (clades), and nodal synapomorphies of our cladograms do not support classical AMD phenotypes as valid transcriptomal subtypes. The majority of the dysregulated gene expressions are specimen-specific or clade-specific (occurring in a small group of specimens) suggesting multiple pathway involvement in conventional clinical subtypes. Gene lists defined by cladogram nodes showed that the AMD-related dysregulations occurring in the neural retina are different from those in RPE-choroidal tissue. Our analysis indicates a complex transcriptional profile of the phenotypes that requires the study of much earlier stages of the disease to elucidate the initial events of AMD.

Keywords: 412 age-related macular degeneration • 535 gene microarray • 473 computational modeling  

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