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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

Hierarchical clustering analysis of gene profiling in SD and TGR rats at 1- and 3-month.Only genes with negative log10 P>10 are shown on the clustering diagram. The diagram shows that TGR 1-month, SD 1- and 3-month have similar gene expression profiling whereas 3-month TGR differs markedly from these three groups. Red indicates high and blue low expression of the single gene compared with the mean. The fold changes in the bar are represented in log2X. A: 1-month TGR; B: 1-month SD; C: 3-month SD; D: 3-month TGR.
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pone-0016865-g001: Hierarchical clustering analysis of gene profiling in SD and TGR rats at 1- and 3-month.Only genes with negative log10 P>10 are shown on the clustering diagram. The diagram shows that TGR 1-month, SD 1- and 3-month have similar gene expression profiling whereas 3-month TGR differs markedly from these three groups. Red indicates high and blue low expression of the single gene compared with the mean. The fold changes in the bar are represented in log2X. A: 1-month TGR; B: 1-month SD; C: 3-month SD; D: 3-month TGR.

Mentions: To identify genes and pathways involved in the development of vasoregression in TGR retinas, gene expression profiling was assessed in TGR and control rats at 1 and 3 months, i.e. before and after initiation of vasoregression, respectively. The Affymetrix GeneChip® for rat expression array 230 2.0 was used. The array comprised of more than 31,000 probe sets for analysing over 30,000 transcripts and variants from over 28,000 rat genes. 3267 genes were significantly upregulated while 2924 genes were significantly downregulated when significance level (p-value) of less than 0.001 was defined as cutoff between TGR and SD rats. Moreover, hierarchical clustering of rat groups was performed based on differential gene expression (Figure 1). Genes of SD rats at 1 and 3 months exhibited similar expression patterns, and had a high comparability to the gene expression patterns of TGR rats at 1 month of age. 3-month old TGR rats demonstrated major changes in gene expression (Figure 2).


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)

Hierarchical clustering analysis of gene profiling in SD and TGR rats at 1- and 3-month.Only genes with negative log10 P>10 are shown on the clustering diagram. The diagram shows that TGR 1-month, SD 1- and 3-month have similar gene expression profiling whereas 3-month TGR differs markedly from these three groups. Red indicates high and blue low expression of the single gene compared with the mean. The fold changes in the bar are represented in log2X. A: 1-month TGR; B: 1-month SD; C: 3-month SD; D: 3-month TGR.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0016865-g001: Hierarchical clustering analysis of gene profiling in SD and TGR rats at 1- and 3-month.Only genes with negative log10 P>10 are shown on the clustering diagram. The diagram shows that TGR 1-month, SD 1- and 3-month have similar gene expression profiling whereas 3-month TGR differs markedly from these three groups. Red indicates high and blue low expression of the single gene compared with the mean. The fold changes in the bar are represented in log2X. A: 1-month TGR; B: 1-month SD; C: 3-month SD; D: 3-month TGR.
Mentions: To identify genes and pathways involved in the development of vasoregression in TGR retinas, gene expression profiling was assessed in TGR and control rats at 1 and 3 months, i.e. before and after initiation of vasoregression, respectively. The Affymetrix GeneChip® for rat expression array 230 2.0 was used. The array comprised of more than 31,000 probe sets for analysing over 30,000 transcripts and variants from over 28,000 rat genes. 3267 genes were significantly upregulated while 2924 genes were significantly downregulated when significance level (p-value) of less than 0.001 was defined as cutoff between TGR and SD rats. Moreover, hierarchical clustering of rat groups was performed based on differential gene expression (Figure 1). Genes of SD rats at 1 and 3 months exhibited similar expression patterns, and had a high comparability to the gene expression patterns of TGR rats at 1 month of age. 3-month old TGR rats demonstrated major changes in gene expression (Figure 2).

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