Article
Gene microarray analysis of experimental glaucomatous retina from cynomologous monkey.
Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Japan.
Investigative Ophthalmology & Visual Science (impact factor:
3.6).
11/2003;
44(10):4347-56.
pp.4347-56
Source: PubMed
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Citations (0)
- Cited In (8)
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Article: Early reduction of microglia activation by irradiation in a model of chronic glaucoma.
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ABSTRACT: Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, the mechanisms leading to onset and progression of the disease remain unknown. Molecular analysis in various glaucoma models has revealed involvement of non-neuronal cell populations, including astrocytes, Mueller glia and microglia, at early stages of glaucoma. High-dose irradiation was reported to have a significant long-term protective effect in the DBA/2J (D2) mouse model of glaucoma, although the cellular and molecular basis for this effect remains unclear. In particular, the acute effects of irradiation on specific cell populations, including non-neuronal cells, in the D2 retina and nerve have not been assessed. Here we report that irradiation induces transient reduction in proliferating microglia within the optic nerve head and glial lamina within the first week post-irradiation. This was accompanied by reduced microglial activation, with no effect on astrocyte gliosis in those regions. At later stages we confirm that early high-dose irradiation of the mouse head results in improvement of axonal structural integrity and anterograde transport function, without reduction of intraocular pressure. Thus reduced microglial activation induced by irradiation at early stages is associated with reduced optic nerve and retinal neurodegeneration in the D2 mouse model of glaucoma.PLoS ONE 01/2012; 7(8):e43602. · 4.09 Impact Factor -
Article: Retinal cell responses to elevated intraocular pressure: a gene array comparison between the whole retina and retinal ganglion cell layer.
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ABSTRACT: To determine and compare gene expression patterns in the whole retina and retinal ganglion cell layer (RGCL) in a rodent glaucoma model. IOP was unilaterally elevated in Brown Norway rats (N = 26) by injection of hypertonic saline and monitored for 5 weeks. A cDNA microarray was used on whole retinas from one group of eyes with extensive optic nerve injury and on RGCL isolated by laser capture microdissection (LCM) from another group with comparable injury, to determine the significantly up- or downregulated genes and gene categories in both groups. Expression changes of selected genes were examined by quantitative reverse transcription-PCR (qPCR) to verify microarray results. Microarray analysis of the whole retina identified 632 genes with significantly changed expression (335 up, 297 down), associated with 9 upregulated and 3 downregulated biological processes. In contrast, the RGCL microarray yielded 3726 genes with significantly changed expression (2003 up, 1723 down), including 60% of those found in whole retina. Thirteen distinct upregulated biological processes were identified in the RGCL, dominated by protein synthesis. Among 11 downregulated processes, axon extension and dendrite morphogenesis and generation of precursor metabolism and energy were uniquely identified in the RGCL. qPCR confirmed significant changes in 6 selected messages in whole retina and 11 in RGCL. Increased Atf3, the most upregulated gene in the RGCL, was confirmed by immunohistochemistry of RGCs. Isolation of RGCL by LCM allows a more refined detection of gene response to elevated pressure and improves the potential of determining cellular mechanisms in RGCs and their supporting cells that could be targets for enhancing RGC survival.Investigative ophthalmology & visual science 06/2010; 51(6):3003-18. · 3.43 Impact Factor -
Article: Neuroinflammation in advanced canine glaucoma.
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ABSTRACT: The pathophysiological events that occur in advanced glaucoma are not well characterized. The principal purpose of this study is to characterize the gene expression changes that occur in advanced glaucoma. Retinal RNA was obtained from canine eyes with advanced glaucoma as well as from healthy eyes. Global gene expression patterns were determined using oligonucleotide microarrays and confirmed by real-time PCR. The presence of tumor necrosis factor (TNF) and its receptors was evaluated by immunolabeling. Finally, we evaluated the presence of serum autoantibodies directed against retinal epitopes using western blot analyses. We identified over 500 genes with statistically significant changes in expression level in the glaucomatous retina. Decreased expression levels were detected for large number of functional groups, including synapse and synaptic transmission, cell adhesion, and calcium metabolism. Many of the molecules with decreased expression levels have been previously shown to be components of retinal ganglion cells. Genes with elevated expression in glaucoma are largely associated with inflammation, such as antigen presentation, protein degradation, and innate immunity. In contrast, expression of many other pro-inflammatory genes, such as interferons or interleukins, was not detected at abnormal levels. This study characterizes the molecular events that occur in the canine retina with advanced glaucoma. Our data suggest that in the dog this stage of the disease is accompanied by pronounced retinal neuroinflammation.Molecular vision 01/2010; 16:2092-108. · 2.20 Impact Factor
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Keywords
control eyes 30 days
experimental glaucoma
expression changes
Expression Sequence Tag
gene expression
Gene expression changes
Gene expression profiles
gene products
human microarray chips
Immunohistochemical studies
laser-induced glaucoma
left eye
microarray analysis
microarray data
mild glaucoma
protein expression
real-time PCR analysis
severe glaucoma
severe glaucomatous retina
trabecular meshwork