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| 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
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| 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.
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| 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.
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| Contributor(s) |
Radeke MJ, Newman AM, Anderson DH, Johnson LV, Hageman GS |
| Citation(s) |
22364233 |
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| Submission date |
Jun 07, 2011 |
| Last update date |
Feb 22, 2018 |
| Contact name |
Monte J. Radeke |
| E-mail(s) |
radeke@ucsb.edu
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| Phone |
805-893-3695
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| Organization name |
University of California, Santa Barbara
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| Department |
Neuroscience Research Institute
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| Lab |
Center for the Study of Macular Degeneration
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| Street address |
Neuroscience Research Institiute
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| City |
Santa Barbara |
| State/province |
CA |
| ZIP/Postal code |
93106-5060 |
| Country |
USA |
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| Platforms (1) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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| Samples (293)
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| Relations |
| BioProject |
PRJNA141019 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29801_RAW.tar |
265.9 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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