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GSE33134
Mus musculus
30 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To investigate pathogenic mechanisms in such instances, we have characterized rod photoreceptor and retinal gene expression changes in response to a defined insult to photoreceptor structure, using the retinal degeneration slow (rds) mouse model. Global gene expression profiling was performed on flow-sorted rds and wild-type rod photoreceptors immediately prior and subsequent to times at which OSs are normally elaborated. Dysregulated genes were identified via microarray hybridization, and selected candidates were validated using quantitative PCR analyses. We identified a single key gene, Egr1, that was dysregulated in a sustained fashion in rds rod photoreceptors and in the retina. Egr1 upregulation was associated with microglial activation and migration, into the outer retina at times subsequent to the major peak of photoreceptor cell death. Interestingly, this response was accompanied by neurotrophic factor upregulation. We hypothesize that activation of Egr1 and neurotrophic factors represents a protective immune mechanism, contributing to the characteristically slow retinal degeneration of the rds mouse model.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To better understand the mechanistic basis of aging and its relationship with retinal degeneration, we examined gene expression changes in aging rod photoreceptors. Rod photoreceptor cell death is a feature of normal retinal aging and is accelerated in many retinal degenerative diseases, including AMD, the leading cause of untreatable adult blindness in the United States and other western countries. To our knowledge, the examination of age-related gene expression changes in a specific neuronal cell-type is novel, and it has allowed us to identify significant age-related changes with better resolution than is possible with whole retina samples. We used flow cytometry and a transgenic mouse with GFP-tagged rod photoreceptors to purify this specific cell population, and gene expression changes were evaluated at three time points using microarrays and quantitative RT-PCR. Our results suggest that aging is progressive, beginning even in young adult mice. Although rod photoreceptors are highly specialized neurons, our analyses revealed changes in consensus pathways of aging, including oxidative phosphorylation and stress responses affecting transcription and inflammation. In addition, we identified stress response processes that may be especially relevant for the aging retina and retinal diseases, such as angiogenesis and nuclear receptor signaling pathways that affect retinoid and lipid metabolism.
Publication Title
Distinct signature of altered homeostasis in aging rod photoreceptors: implications for retinal diseases.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Our data suggest that CNTF remodels the transcription profile of Mller (glial) cells leading to induction of networks associated with transcription, cell cycle regulation and inflammatory response. CNTF also appears to function as an inducer of gliosis in the retina. These studies provide new insights into the biological functions of cytokines in the retina.
Publication Title
Ciliary neurotrophic factor induces genes associated with inflammation and gliosis in the retina: a gene profiling study of flow-sorted, Müller cells.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Myocilin, a causative gene for open-angle glaucoma, encodes a secreted glycoprotein of unknown function. To elucidate its function(s), we produced a stably transfected HEK293 cell line expressing myocilin and compared the expression profiles between the myocilin-expressing cell line and a vector control cell line using Affymetrix GeneChip U133 plus 2.0 array. A significant portion of differentially-expressed genes in the myocilin-expressing cells was associated with cell growth and cell death, suggesting that myocilin may have an important role regulating cell growth/survival..
Publication Title
Myocilin regulates cell proliferation and survival.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To better understand the function of CD8aa Tregs, we have recently characterized several CD8aa+TCRab+ T cell clones and lines that are physiologically primed and are involved in recovery and protection from EAE (REF). In this report, we present a comparison of global gene expression patterns in CD8aa Tregs versus OT-1 CD8aa+TCRab+ T cells. The results of microarray data analysis are confirmed by real-time PCR and flow cytometry for better accuracy and phenotype expression. Our study reveals a unique gene signature in the CD8aa Tregs, including enhanced expression of several inhibitory molecules associated with the maintenance of peripheral T cell homeostasis. The identification of differentially expressed molecules by CD8aa Tregs should facilitate future functional studies in this area.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors has not been previously investigated. Here we report the lens phenotypes of Notch2 conditionally mutant mice, which exhibited severe microphthalmia, reduced pupillary openings, disrupted fiber cell morphology, eventual loss of the anterior epithelium, fiber cell dysgenesis, and cataracts. Notch2 mutants also had a persistent lens stalk phenotype at E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2) and Trp63 (p63) that negatively regulates Wnt signaling. Although removal of Notch2 phenocopied the increased proportion of fiber cells of Rbpj and Jag1 conditional mutant lenses, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. Instead, we found that the Notch2 normally blocks progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
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