TEXT FROM GEO
+ +Genome-wide assessment of gene expression changes was performed in DBA/2J mice. The optic nerve head and retina from 40 DBA/2J eyes at 10.5 months of age were separately profiled. These eyes were selected as they encompassed a range of glaucoma severity. Two control groups were also included; 10 eyes from 10.5 months old D2-Gpnmb+ mice (age and strain matched, no glaucoma control) and 10 eyes from 4.5 months old DBA/2J mice (young, pre-glaucoma).
+ +In this study that was specifically designed to identify early stages of glaucoma in DBA/2J mice, we used genome-wide expression profiling and a series of computational methods. Our methods successfully subdivided eyes with no detectable glaucoma by conventional assays into molecularly defined stages of disease. These stages represent a temporally ordered sequence of glaucoma states. Using an array of tools, we then determined networks and biological processes that are altered at these early stages. Our strategy proved very sensitive, suggesting that similar approaches will be valuable for uncovering early processes in other complex, later-onset diseases. Early changes included upregulation of both the complement cascade and endothelin system, and so we tested the therapeutic value of separately inhibiting them. Mice with a mutation in the complement component 1a gene (C1qa) were robustly protected from glaucoma with the protection being among the greatest reported. Similarly, inhibition of the endothelin system was strongly protective. Since EDN2 is potently vasoconstrictive and was produced by microglial/macrophages, our data provide a novel link between these cell types and vascular dysfunction in glaucoma. Targeting early events such as the upregulation of the complement and endothelin pathways may provide effective new treatments for human glaucoma. (text above from GEO http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26299)
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diff --git a/general/datasets/Dba2j_onh_1212/summary.rtf b/general/datasets/Dba2j_onh_1212/summary.rtf new file mode 100644 index 0000000..09c8a43 --- /dev/null +++ b/general/datasets/Dba2j_onh_1212/summary.rtf @@ -0,0 +1,58 @@ +
This is an experimental glaucoma gene expression data set of retinal tissue entered into GeneNetwork by Dr. Eldon Geisert and Robert Williams in which BXD strains have been "highjacked" with experimental and control gene expression data generated by Drs Gareth Howell, Simon John, and colleagues at the Jackson Laboratory. These data were originally entered into GeneNetwork Sept 20, 2011.
+ +Please see the original paper by Howell et al (2011): http://www.jci.org/articles/view/44646 and GEO data at NCBI.
+ +Gareth R. Howell, Danilo G. Macalinao, Gregory L. Sousa, Michael Walden, Ileana Soto, Stephen C. Kneeland, Jessica M. Barbay, Benjamin L. King, Jeffrey K. Marchant, Matthew Hibbs, Beth Stevens, Ben A. Barres, Abbot F. Clark, Richard T. Libby, Simon S (2011) Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma. J Clin Invest. 121:1429–1444
+ +Each strain corresponds to a particular retinal sample as shown below (note that we have not included ten "preglaucoma control" samples, see http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26299
+ +