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Mol Vis. 2007 Oct 5;13:1892-901.

Ischemic preconditioning alters the pattern of gene expression changes in response to full retinal ischemia.

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  • 1Department of Molecular Ophthalmogenetics, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands. w.kamphuis@nin.knaw.nl

Abstract

PURPOSE:

Ischemic conditions in the retina have been implicated in several retinopathological conditions. Experimentally induced ischemia for 60 min followed by reperfusion leads to a loss of neurons in the inner retina. In contrast, a 5 min ischemic episode triggers a series of alterations that protect the retina against the damaging effects of a subsequent 60 min ischemic insult. This phenomenon is called ischemic preconditioning (IPC). To study the changes altered by IPC, we assessed the gene expression patterns in the rat retina after ischemia (60 min) followed by reperfusion (I/R) and compared these to the gene expression patterns after ischemia/reperfusion in preconditioned animals (IPC-I/R).

METHODS:

Changes in gene expression were studied, by means of microarrays, at 1, 2, 6, and 12 h after I/R in naíve and preconditioned animals. To identify functional pathways of interest, we used significantly regulated genes as input for gene ontology analysis. Microarray results were validated by real-time quantitative PCR.

RESULTS:

Most genes that were altered by I/R showed a comparable change in both naíve and preconditioned animals. Differential expression was found for a total of 1312 genes of the 20,280 features (6.4%) present on the array with a differential change of 1.7 fold or more. The list of genes with a differential change was characterized by a statistically significant overrepresentation of genes associated to the gene ontology terms tRNA aminoacylation (with a decreased expression due to preconditioning), immune response (with most genes upregulated), and apoptosis (mixed direction of changes). The results of quantitative PCR assays were in agreement with the microarray data.

CONCLUSIONS:

The response of several functional groups of genes on ischemia was altered by a preconditioning stimulus. Most prominent differences were found for the group of genes encoding for aminoacyl-tRNA synthetases (ARSs), which is in line with the previously observed decreased expression of ARSs after induction of preconditioning. Our observations indicate that activation of translational activity may be a mediator of ischemia-associated damage in the retina, and IPC may prevent activation of this mechanism. An altered expression of genes implicated in immune response and in apoptosis may also be involved in effectuating IPC.

PMID:
17960128
[PubMed - indexed for MEDLINE]
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