Open Access Highly Accessed Research article

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

Markus Thiersch1, Wolfgang Raffelsberger2, Rico Frigg1, Marijana Samardzija1, Andreas Wenzel1, Olivier Poch2 and Christian Grimm1*

Author Affiliations

1 Lab of Retinal Cell Biology, Dept Ophthalmology, University of Zurich, Switzerland

2 Laboratoire de BioInformatique et Génomique Intégrative, Institut de Genetique et de Biologie Moleculaire et Cellulaire, 67404 Illkirch, France

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BMC Genomics 2008, 9:73  doi:10.1186/1471-2164-9-73

Published: 8 February 2008



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.


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.


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.