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Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection

BACKGROUND: Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1α in the retina and strongly protects photoreceptors in an animal model of ligh...

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Autores principales: Thiersch, Markus, Raffelsberger, Wolfgang, Frigg, Rico, Samardzija, Marijana, Wenzel, Andreas, Poch, Olivier, Grimm, Christian
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270833/
https://www.ncbi.nlm.nih.gov/pubmed/18261226
http://dx.doi.org/10.1186/1471-2164-9-73
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author Thiersch, Markus
Raffelsberger, Wolfgang
Frigg, Rico
Samardzija, Marijana
Wenzel, Andreas
Poch, Olivier
Grimm, Christian
author_facet Thiersch, Markus
Raffelsberger, Wolfgang
Frigg, Rico
Samardzija, Marijana
Wenzel, Andreas
Poch, Olivier
Grimm, Christian
author_sort Thiersch, Markus
collection PubMed
description BACKGROUND: Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1α in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration. To address the molecular mechanisms of the protection, we analyzed the transcriptome of the hypoxic retina using microarrays and real-time PCR. RESULTS: Hypoxic exposure induced a marked alteration in the retinal transcriptome with significantly different expression levels of 431 genes immediately after hypoxic exposure. The normal expression profile was restored within 16 hours of reoxygenation. Among the differentially regulated genes, several candidates for neuroprotection were identified like metallothionein-1 and -2, the HIF-1 target gene adrenomedullin and the gene encoding the antioxidative and cytoprotective enzyme paraoxonase 1 which was previously not known to be a hypoxia responsive gene in the retina. The strongly upregulated cyclin dependent kinase inhibitor p21 was excluded from being essential for neuroprotection. CONCLUSION: Our data suggest that neuroprotection after hypoxic preconditioning is the result of the differential expression of a multitude of genes which may act in concert to protect visual cells against a toxic insult.
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spelling pubmed-22708332008-03-21 Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection Thiersch, Markus Raffelsberger, Wolfgang Frigg, Rico Samardzija, Marijana Wenzel, Andreas Poch, Olivier Grimm, Christian BMC Genomics Research Article BACKGROUND: Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1α in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration. To address the molecular mechanisms of the protection, we analyzed the transcriptome of the hypoxic retina using microarrays and real-time PCR. RESULTS: Hypoxic exposure induced a marked alteration in the retinal transcriptome with significantly different expression levels of 431 genes immediately after hypoxic exposure. The normal expression profile was restored within 16 hours of reoxygenation. Among the differentially regulated genes, several candidates for neuroprotection were identified like metallothionein-1 and -2, the HIF-1 target gene adrenomedullin and the gene encoding the antioxidative and cytoprotective enzyme paraoxonase 1 which was previously not known to be a hypoxia responsive gene in the retina. The strongly upregulated cyclin dependent kinase inhibitor p21 was excluded from being essential for neuroprotection. CONCLUSION: Our data suggest that neuroprotection after hypoxic preconditioning is the result of the differential expression of a multitude of genes which may act in concert to protect visual cells against a toxic insult. BioMed Central 2008-02-08 /pmc/articles/PMC2270833/ /pubmed/18261226 http://dx.doi.org/10.1186/1471-2164-9-73 Text en Copyright © 2008 Thiersch et al; http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Thiersch, Markus
Raffelsberger, Wolfgang
Frigg, Rico
Samardzija, Marijana
Wenzel, Andreas
Poch, Olivier
Grimm, Christian
Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection
title Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection
title_full Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection
title_fullStr Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection
title_full_unstemmed Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection
title_short Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection
title_sort analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270833/
https://www.ncbi.nlm.nih.gov/pubmed/18261226
http://dx.doi.org/10.1186/1471-2164-9-73
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