Mus musculus
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ABSTRACT:
PROVIDER: PRJNA156985 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Microarray Analysis of Retinal Gene Expression in the DBA/2J Model of Glaucoma
| PRJNA93629 | ENA
Project description: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. 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).
2011-04-15 | E-GEOD-26299 | biostudies-arrayexpress
Project description:Purpose: The DBA/2J mouse is a model for secondary angle-closure glaucoma due to iris atrophy and pigment dispersion, which ultimately leads to increased intraocular pressure (IOP). We sought to correlate changes in retinal gene expression with glaucoma-like pathology by performing microarray analysis of retinal RNA from DBA/2J mice at 3 months before disease onset, and at 8 months, after IOP elevation. Methods: IOP was monitored monthly in DBA/2J animals by Tono-Pen and animals with normal (3 months) or elevated IOP (8 months) were identified. RNA was prepared from 3 individual retinas at each age, and the RNA was amplified and used to generate biotin-labeled probe for high density mouse Affymetrix arrays (U430.2). A subset of genes was selected for confirmation by quantitative RT-PCR using independent retina samples from DBA/2J animals at 3, 5 and 8 months of age, and compared to retinas from C57BL/6J control animals at 3 and 8 months. Results: There were changes in expression of 68 genes, with 32 genes increasing and 36 genes decreasing at 8 months versus 3 months. Upregulated genes were associated with immune response, glial activation, signaling and gene expression, while down-regulated genes included multiple crystallin genes. Significant changes in 9 upregulated genes and 2 downregulated genes were confirmed by quantitative RT-PCR, with some showing changes in expression by 5 months. Conclusions: DBA/2J retina shows evidence for glial activation and an immune-related response following IOP elevation, similar to what has been reported following acute elevation of IOP in other models. Keywords: retina, glaucoma, DBA/2J, elevated intraocular pressure
2005-11-04 | GSE3554 | GEO
Project description:Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve. Genome-wide assessment of gene expression changes was performed in DBA/2J-Gpnmb+, DBA/2J mice and irradiated DBA/2J mice at 8.5 and 10.5 months of age.
2012-03-28 | GSE36833 | GEO
Project description:Expression profiling of F2 progenies from C57BL/6J x DBA/2J
| PRJNA117717 | ENA
Project description:Purpose: The DBA/2J mouse is a model for secondary angle-closure glaucoma due to iris atrophy and pigment dispersion, which ultimately leads to increased intraocular pressure (IOP). We sought to correlate changes in retinal gene expression with glaucoma-like pathology by performing microarray analysis of retinal RNA from DBA/2J mice at 3 months before disease onset, and at 8 months, after IOP elevation. Methods: IOP was monitored monthly in DBA/2J animals by Tono-Pen and animals with normal (3 months) or elevated IOP (8 months) were identified. RNA was prepared from 3 individual retinas at each age, and the RNA was amplified and used to generate biotin-labeled probe for high density mouse Affymetrix arrays (U430.2). A subset of genes was selected for confirmation by quantitative RT-PCR using independent retina samples from DBA/2J animals at 3, 5 and 8 months of age, and compared to retinas from C57BL/6J control animals at 3 and 8 months. Results: There were changes in expression of 68 genes, with 32 genes increasing and 36 genes decreasing at 8 months versus 3 months. Upregulated genes were associated with immune response, glial activation, signaling and gene expression, while down-regulated genes included multiple crystallin genes. Significant changes in 9 upregulated genes and 2 downregulated genes were confirmed by quantitative RT-PCR, with some showing changes in expression by 5 months. Conclusions: DBA/2J retina shows evidence for glial activation and an immune-related response following IOP elevation, similar to what has been reported following acute elevation of IOP in other models. IOP was monitored monthly in DBA/2J animals by Tono-Pen and animals with normal (3 months) or elevated IOP (8 months) were identified. RNA was prepared from 3 individual retinas at each age, and the RNA was amplified and used to generate biotin-labeled probe for high density mouse Affymetrix arrays (U430.2). A subset of genes was selected for confirmation by quantitative RT-PCR using independent retina samples from DBA/2J animals at 3, 5 and 8 months of age, and compared to retinas from C57BL/6J control animals at 3 and 8 months.
2007-12-15 | E-GEOD-3554 | biostudies-arrayexpress
Project description:Comparative analysis of gene expression in A/J CB versus DBA/2J
| PRJNA96321 | ENA
Project description:Hepatic expression data between C57BL/6J and DBA/2J mice
| PRJNA118319 | ENA