Global Gene Expression Profiling of Ischemic Preconditioning in the Rat Retina

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2007 Jul 27

PMID 17653046

Citations 22

Authors

W Kamphuis

F Dijk

S Van Soest

A A B Bergen

Affiliations

Soon will be listed here.

Abstract

Purpose: To obtain and analyze the gene expression changes after ischemic preconditioning (IPC) in the rat retina.

Methods: Ischemic damage to the inner retina can be prevented by a short, non-deleterious, ischemic insult of 5 min applied 24 h preceding a full ischemic insult of 60 min; a phenomenon termed tolerance or IPC. The time course of changes in gene expression after induction of IPC was assessed by 22K oligonucleotide microarrays, followed by real-time quantitative polymerase chain reaction (qPCR) validation. Functional pathways of interest were identified by Gene Ontology-term analysis.

Results: Histology confirmed that IPC induction by 5 min of retinal ischemia results in a complete protection against the neurodegenerative effects of a 60 min ischemic period applied 24 or 48 h later. The microarray analysis revealed differential expression of 104 known genes at one or more time points between 1 h and 7 days after IPC. The group of altered genes contained a significant overrepresentation of genes involved in aminoacyl-tRNA synthetase activity (Iars, Lars, Cars, Yars, Gars, Tars), amino acid transport (Slc3a2, Slc6a6, Slc7a1, Slc38a2), regulation of transcription (including Egr1, Egr4, Nr4a1, Nr4a3, c-fos), and cell death (including Anxa1, Trib3). qPCR assays on cDNA of individual animals confirmed the microarray results.

Conclusions: Endogenous neuroprotection, provoked by ischemic preconditioning is associated with changes in transcript levels of several functionally-related groups of genes. During the time window of effective protection, transcript levels of genes encoding for aminoacyl-tRNA synthetases and for amino acid transport are reduced. These changes suggest that a reduction of translational activity may play a significant role in preconditioning-mediated neuroprotection.

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References

Roberts C, Nelson B, Marton M, STOUGHTON R, Meyer M, Bennett H . Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles. Science. 2000; 287(5454):873-80. DOI: 10.1126/science.287.5454.873. View

Tsujikawa A, Ogura Y, Hiroshiba N, Miyamoto K, Kiryu J, Honda Y . In vivo evaluation of leukocyte dynamics in retinal ischemia reperfusion injury. Invest Ophthalmol Vis Sci. 1998; 39(5):793-800. View

Hughes T, Marton M, Jones A, Roberts C, STOUGHTON R, Armour C . Functional discovery via a compendium of expression profiles. Cell. 2000; 102(1):109-26. DOI: 10.1016/s0092-8674(00)00015-5. View

Hughes T, Mao M, Jones A, Burchard J, Marton M, Shannon K . Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer. Nat Biotechnol. 2001; 19(4):342-7. DOI: 10.1038/86730. View

Grunwald J, Hariprasad S, Dupont J . Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects. Am J Ophthalmol. 2001; 132(1):63-9. DOI: 10.1016/s0002-9394(01)00871-6. View

Nonaka A, Kiryu J, Tsujikawa A, Yamashiro K, Nishijima K, Miyamoto K . Inhibitory effect of ischemic preconditioning on leukocyte participation in retinal ischemia-reperfusion injury. Invest Ophthalmol Vis Sci. 2001; 42(10):2380-5. View

Osborne N, Melena J, Chidlow G, Wood J . A hypothesis to explain ganglion cell death caused by vascular insults at the optic nerve head: possible implication for the treatment of glaucoma. Br J Ophthalmol. 2001; 85(10):1252-9. PMC: 1723727. DOI: 10.1136/bjo.85.10.1252. View

Lam T, Abler A, Tso M . Apoptosis and caspases after ischemia-reperfusion injury in rat retina. Invest Ophthalmol Vis Sci. 1999; 40(5):967-75. View

Li B, Roth S . Retinal ischemic preconditioning in the rat: requirement for adenosine and repetitive induction. Invest Ophthalmol Vis Sci. 1999; 40(6):1200-16. View

10.

Nickells R . Apoptosis of retinal ganglion cells in glaucoma: an update of the molecular pathways involved in cell death. Surv Ophthalmol. 1999; 43 Suppl 1:S151-61. DOI: 10.1016/s0039-6257(99)00029-6. View

11.

Proud C . eIF2 and the control of cell physiology. Semin Cell Dev Biol. 2005; 16(1):3-12. DOI: 10.1016/j.semcdb.2004.11.004. View

12.

Whitlock N, Lindsey K, Agarwal N, Crosson C, Ma J . Heat shock protein 27 delays Ca2+-induced cell death in a caspase-dependent and -independent manner in rat retinal ganglion cells. Invest Ophthalmol Vis Sci. 2005; 46(3):1085-91. DOI: 10.1167/iovs.04-0042. View

13.

Whitlock N, Agarwal N, Ma J, Crosson C . Hsp27 upregulation by HIF-1 signaling offers protection against retinal ischemia in rats. Invest Ophthalmol Vis Sci. 2005; 46(3):1092-8. DOI: 10.1167/iovs.04-0043. View

14.

Brandish P, Su M, Holder D, Hodor P, Szumiloski J, Kleinhanz R . Regulation of gene expression by lithium and depletion of inositol in slices of adult rat cortex. Neuron. 2005; 45(6):861-72. DOI: 10.1016/j.neuron.2005.02.006. View

15.

Helton R, Cui J, Scheel J, Ellison J, Ames C, Gibson C . Brain-specific knock-out of hypoxia-inducible factor-1alpha reduces rather than increases hypoxic-ischemic damage. J Neurosci. 2005; 25(16):4099-107. PMC: 6724950. DOI: 10.1523/JNEUROSCI.4555-04.2005. View

16.

Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H . TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J. 2005; 24(6):1243-55. PMC: 556400. DOI: 10.1038/sj.emboj.7600596. View

17.

Grimm C, Hermann D, Bogdanova A, Hotop S, Kilic U, Wenzel A . Neuroprotection by hypoxic preconditioning: HIF-1 and erythropoietin protect from retinal degeneration. Semin Cell Dev Biol. 2005; 16(4-5):531-8. DOI: 10.1016/j.semcdb.2005.03.004. View

18.

Naylor M, Bowen K, Sailor K, Dempsey R, Vemuganti R . Preconditioning-induced ischemic tolerance stimulates growth factor expression and neurogenesis in adult rat hippocampus. Neurochem Int. 2005; 47(8):565-72. DOI: 10.1016/j.neuint.2005.07.003. View

19.

Pavitt G . eIF2B, a mediator of general and gene-specific translational control. Biochem Soc Trans. 2005; 33(Pt 6):1487-92. DOI: 10.1042/BST0331487. View

20.

Bluthgen N, Brand K, Cajavec B, Swat M, Herzel H, Beule D . Biological profiling of gene groups utilizing Gene Ontology. Genome Inform. 2005; 16(1):106-15. View