Journal
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
Volume 58, Issue 3, Pages 247-254Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1369/jhc.2009.953786
Keywords
hypoxia; retina; hypoxia-inducible factor; VEGF; glucose transporter; carbonic anhydrase
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Funding
- Dutch Diabetes Fund [1998.131]
- Edward and Marianne Blaauw Foundation
- Landelijke Stichting voor Blinden en Slechtzienden, Utrecht
- Blindenpenning Foundation, Amsterdam
- Society for the Blind, Rotterdam
- Society for the Blind, Gelderland, The Netherlands
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A unique feature of the retina is the presence of photoreceptors, which require an enormous amount of oxygen for the conversion of light to an electrical signal. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a transcription factor that is the master regulator of cellular adaptation to low oxygen tension. Only in hypoxic conditions is HIF-1 alpha protein stabilized and translocated to the nucleus, where it induces transcription of target genes involved in oxygen delivery and energy metabolism. We hypothesized that HIF-1 alpha is constitutively stabilized and active in the normal human retina. We investigated the cellular distribution of HIF-1 alpha and the expression of its downstream targets, vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT-1), and carbonic anhydrase IX (CAIX), by immunohistochemistry and immunoblotting in the retina of normal rats and human donor eyes. Both human and rat retinas displayed prominent staining of HIF-1 alpha. in nuclei of most cell types in inner and outer nuclear layers and the ganglion cell layer, a cellular distribution pattern which was confirmed in human retina by immunoblotting of nuclear extracts. A negative correlation was found between HIF-1 alpha protein levels and postmortem times. In human retina, staining of VEGF, GLUT-1, and CAIX was found. Our observations indicate that active HIF-1 signaling occurs constitutively in the normal human and rat retina, suggesting that HIF-1 has a physiological role in the retina. (J Histochem Cytochem 58:247-254, 2010)
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