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Series GSE29801 Query DataSets for GSE29801
Status Public on Feb 14, 2012
Title Systems-level analysis of age-related macular degeneration reveals global and subtype-specific functional pathways
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Age-related macular degeneration (AMD) is a leading cause of human blindness in developed countries. While significant inroads have been made over the past decade, an integrated description of the molecular mechanisms underlying AMD has yet to emerge. Here we describe a systems-level transcriptome analysis of the retina and retinal pigmented epithelium (RPE)-choroid complex from 31 normal, 26 AMD, and 11 potential pre-AMD human eyes derived from the University of Iowa. Our analysis identifies cell-mediated immune responses as the central feature of dry AMD, wet AMD, and geographic atrophy (GA), and we confirm this finding using a second cohort of donor eyes obtained from the Lion's Eye Bank of Oregon. In addition, in the RPE-choroid, we identify the major up-regulated pathways in GA and wet AMD as apoptosis and angiogenesis, respectively. In the retina, a graded up-regulation of wound response, complement, and neurogenesis pathway genes strongly correlates with advanced stages of AMD, in parallel with a progressive down-regulation of key phototransduction processes. Finally, using expression signatures enriched in functional pathways, we assemble two detailed AMD interactomes that highlight modular gene expression programs that delineate and interconnect dry, wet, and GA AMD subtypes across both RPE-choroid and retina tissues. In total, these interactomes are comprised of over 150 genes of which 23 have been previously associated with AMD. These data provide new insights into the expression landscape of AMD pathophysiology, and reveal numerous new targets for AMD pharmaceuticals and diagnostics.
 
Overall design 177 samples from the macular or extramacular region of human donor eye RPE-choroids and 118 samples from the macular or extramacular region of human donor retina with no reported ocular disease, possible preclinical AMD or AMD were analyzed using a two-color universal reference design. The reference RNA was comprised of a 1:1 mixture of pooled RPE-choroid and retina RNA from normal and AMD eyes. Except for two samples, no replicates were performed. The dyes used to label the experimental samples and the reference samples were alternated.

The non-Iowa donor eye data was used as a second cohort for verification purposes of global (i.e., non-subtype-specific) expression.
 
Contributor(s) Radeke MJ, Newman AM, Anderson DH, Johnson LV, Hageman GS
Citation(s) 22364233
Submission date Jun 07, 2011
Last update date Feb 22, 2018
Contact name Monte J. Radeke
E-mail(s) monte.radeke@lifesci.ucsb.edu
Phone 805-893-3695
Organization name University of California, Santa Barbara
Department Neuroscience Research Institute
Lab Center for the Study of Macular Degeneration
Street address Neuroscience Research Institiute
City Santa Barbara
State/province CA
ZIP/Postal code 93106-5060
Country USA
 
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (293)
GSM738433 RPEChoroid_1
GSM738434 RPEChoroid_2
GSM738435 RPEChoroid_3
Relations
BioProject PRJNA141019

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Supplementary file Size Download File type/resource
GSE29801_RAW.tar 265.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data provided as supplementary file
Processed data included within Sample table
Processed data provided as supplementary file

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