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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...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2008
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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. |
format | Text |
id | pubmed-2270833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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