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Series GSE26299 Query DataSets for GSE26299
Status Public on Apr 15, 2011
Title Gene expression profiling in DBA/2J glaucoma
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
 
Overall design 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).
 
Contributor(s) Howell GR, John SW
Citation(s) 21383504
Submission date Dec 23, 2010
Last update date Feb 11, 2019
Contact name Gareth Rhys Howell
E-mail gareth.howell@jax.org
Phone 207 288 6572
Fax 207 288 6078
Organization name The Jackson Laboratory
Street address 600 Main Street
City Mount Desert
ZIP/Postal code 04609
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (108)
GSM685892 No or early 1 rep1 (OHN)
GSM685893 No or early 1 rep2 (OHN)
GSM685894 No or early 1 rep3 (OHN)
Relations
BioProject PRJNA135129

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE26299_ONH_clustering_data.txt.gz 115.7 Kb (ftp)(http) TXT
GSE26299_RAW.tar 368.9 Mb (http)(custom) TAR (of CEL)
GSE26299_Retina_clustering_data.txt.gz 143.9 Kb (ftp)(http) TXT
Raw data provided as supplementary file
Processed data included within Sample table

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