Ischemic preconditioning alters the pattern of gene expressionchanges in response to full retinal ischemia

[摘要] Purpose: Ischemic conditions in the retina have been implicated inseveral retinopathological conditions. Experimentally induced ischemiafor 60 min followed by reperfusion leads to a loss of neurons in theinner retina. In contrast, a 5 min ischemic episode triggers a series ofalterations that protect the retina against the damaging effects of asubsequent 60 min ischemic insult. This phenomenon is called ischemicpreconditioning (IPC). To study the changes altered by IPC, we assessedthe gene expression patterns in the rat retina after ischemia (60 min)followed by reperfusion (I/R) and compared these to the gene expressionpatterns after ischemia/reperfusion in preconditioned animals(IPC-I/R).Methods: Changes in gene expression were studied, by means ofmicroarrays, at 1, 2, 6, and 12 h after I/R in naíve andpreconditioned animals. To identify functional pathways of interest, weused 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 comparablechange in both naíve and preconditioned animals. Differentialexpression 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 ormore. The list of genes with a differential change was characterized bya statistically significant overrepresentation of genes associated tothe gene ontology terms tRNA aminoacylation (with a decreased expressiondue to preconditioning), immune response (with most genes upregulated),and apoptosis (mixed direction of changes). The results of quantitativePCR assays were in agreement with the microarray data.Conclusions: The response of several functional groups of genes onischemia was altered by a preconditioning stimulus. Most prominentdifferences were found for the group of genes encoding foraminoacyl-tRNA synthetases (ARSs), which is in line with the previouslyobserved decreased expression of ARSs after induction ofpreconditioning. Our observations indicate that activation oftranslational activity may be a mediator of ischemia-associated damagein the retina, and IPC may prevent activation of this mechanism. Analtered expression of genes implicated in immune response and inapoptosis may also be involved in effectuating IPC.

[学科分类] 生物化学/生物物理