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Gene expression profiling of vasoregression in the retina--involvement of microglial cells.

Feng Y, Wang Y, Li L, Wu L, Hoffmann S, Gretz N, Hammes HP - PLoS ONE (2011)

Bottom Line: Of the 157 genes regulated more than twofold, the MHC class II invariant chain CD74 yielded the strongest upregulation, and was allocated to activated microglial cells close to the vessels undergoing vasoregression.Pathway clustering identified genes of the immune system including inflammatory signaling, and components of the complement cascade upregulated during vasoregression.Together, our data suggest that microglial cells involved in retinal immune response participate in the initiation of vasoregression in the retina.

View Article: PubMed Central - PubMed

Affiliation: 5 Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

ABSTRACT
Vasoregression is a hallmark of vascular eye diseases but the mechanisms involved are still largely unknown. We have recently characterized a rat ciliopathy model which develops primary photoreceptor degeneration and secondary vasoregression. To improve the understanding of secondary vasoregression in retinal neurodegeneration, we used microarray techniques to compare gene expression profiles in this new model before and after retinal vasoregression. Differential gene expression was validated by quantitative RT-PCR, Western blot and immunofluorescence. Of the 157 genes regulated more than twofold, the MHC class II invariant chain CD74 yielded the strongest upregulation, and was allocated to activated microglial cells close to the vessels undergoing vasoregression. Pathway clustering identified genes of the immune system including inflammatory signaling, and components of the complement cascade upregulated during vasoregression. Together, our data suggest that microglial cells involved in retinal immune response participate in the initiation of vasoregression in the retina.

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Related in: MedlinePlus

Antigen presentation and complement component response signaling predicted by Ingenuity Pathway Analysis in the TGR.All genes whose mRNA expression levels were differentially regulated in the TGR at 3 months are highlighted in red. Genes validated by real-time PCR are marked by green dotted circles. Symbols depict different gene functions. The upward facing fork shape represents transmembrane receptor, the right facing forceps shape represents peptidase, the dumbell shape represents transcription regulator.
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pone-0016865-g003: Antigen presentation and complement component response signaling predicted by Ingenuity Pathway Analysis in the TGR.All genes whose mRNA expression levels were differentially regulated in the TGR at 3 months are highlighted in red. Genes validated by real-time PCR are marked by green dotted circles. Symbols depict different gene functions. The upward facing fork shape represents transmembrane receptor, the right facing forceps shape represents peptidase, the dumbell shape represents transcription regulator.

Mentions: Additionally, to examine the potential biological relevance of the transcriptome response during vasoregression, differentially expressed genes were classified according to their biological processes defined in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Functional analysis using GO revealed that a number of specific pathways were actively involved in the development of vasoregression in TGR rats at 3 months. Fourty pathways in GO were significantly upregulated during vasoregression in 3-month TGR compared with 1-month TGR and 3-month SD retinas. On the other hand, a total of five pathways were upregulated in KEGG. Furthermore, genes involved in the immune system including inflammatory and complementary response, cell signalling via receptors, especially protein tyrosine kinase activity, exhibited strong correlation with vasoregression. Some genes were shared by different pathways, such as CD74 antigen in the immune effector process, in antigen processing and presentation, in inflammatory response and in cytokine binding; CCAAT/enhancer binding protein beta (CEBPB) was shared in pathways of the immune response, in defence response and in inflammatory response. Figure 3 depicts the two central pathways, i.e. the antigen presentation pathways, and the acute response pathway, and their relationships.


Gene expression profiling of vasoregression in the retina--involvement of microglial cells.

Feng Y, Wang Y, Li L, Wu L, Hoffmann S, Gretz N, Hammes HP - PLoS ONE (2011)

Antigen presentation and complement component response signaling predicted by Ingenuity Pathway Analysis in the TGR.All genes whose mRNA expression levels were differentially regulated in the TGR at 3 months are highlighted in red. Genes validated by real-time PCR are marked by green dotted circles. Symbols depict different gene functions. The upward facing fork shape represents transmembrane receptor, the right facing forceps shape represents peptidase, the dumbell shape represents transcription regulator.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040753&req=5

pone-0016865-g003: Antigen presentation and complement component response signaling predicted by Ingenuity Pathway Analysis in the TGR.All genes whose mRNA expression levels were differentially regulated in the TGR at 3 months are highlighted in red. Genes validated by real-time PCR are marked by green dotted circles. Symbols depict different gene functions. The upward facing fork shape represents transmembrane receptor, the right facing forceps shape represents peptidase, the dumbell shape represents transcription regulator.
Mentions: Additionally, to examine the potential biological relevance of the transcriptome response during vasoregression, differentially expressed genes were classified according to their biological processes defined in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Functional analysis using GO revealed that a number of specific pathways were actively involved in the development of vasoregression in TGR rats at 3 months. Fourty pathways in GO were significantly upregulated during vasoregression in 3-month TGR compared with 1-month TGR and 3-month SD retinas. On the other hand, a total of five pathways were upregulated in KEGG. Furthermore, genes involved in the immune system including inflammatory and complementary response, cell signalling via receptors, especially protein tyrosine kinase activity, exhibited strong correlation with vasoregression. Some genes were shared by different pathways, such as CD74 antigen in the immune effector process, in antigen processing and presentation, in inflammatory response and in cytokine binding; CCAAT/enhancer binding protein beta (CEBPB) was shared in pathways of the immune response, in defence response and in inflammatory response. Figure 3 depicts the two central pathways, i.e. the antigen presentation pathways, and the acute response pathway, and their relationships.

Bottom Line: Of the 157 genes regulated more than twofold, the MHC class II invariant chain CD74 yielded the strongest upregulation, and was allocated to activated microglial cells close to the vessels undergoing vasoregression.Pathway clustering identified genes of the immune system including inflammatory signaling, and components of the complement cascade upregulated during vasoregression.Together, our data suggest that microglial cells involved in retinal immune response participate in the initiation of vasoregression in the retina.

View Article: PubMed Central - PubMed

Affiliation: 5 Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

ABSTRACT
Vasoregression is a hallmark of vascular eye diseases but the mechanisms involved are still largely unknown. We have recently characterized a rat ciliopathy model which develops primary photoreceptor degeneration and secondary vasoregression. To improve the understanding of secondary vasoregression in retinal neurodegeneration, we used microarray techniques to compare gene expression profiles in this new model before and after retinal vasoregression. Differential gene expression was validated by quantitative RT-PCR, Western blot and immunofluorescence. Of the 157 genes regulated more than twofold, the MHC class II invariant chain CD74 yielded the strongest upregulation, and was allocated to activated microglial cells close to the vessels undergoing vasoregression. Pathway clustering identified genes of the immune system including inflammatory signaling, and components of the complement cascade upregulated during vasoregression. Together, our data suggest that microglial cells involved in retinal immune response participate in the initiation of vasoregression in the retina.

Show MeSH
Related in: MedlinePlus