TY - JOUR
T1 - Active HIF-1 in the normal human retina
AU - Hughes, John M.
AU - Groot, Arjan J.
AU - Van Groep, Petra Der
AU - Sersansie, René
AU - Vooijs, Marc
AU - Van Diest, Paul J.
AU - Van Noorden, Cornelis J.F.
AU - Schlingemann, Reinier O.
AU - Klaassen, Ingeborg
PY - 2010/3
Y1 - 2010/3
N2 - 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-1α) is a transcription factor that is the master regulator of cellular adaptation to low oxygen tension. Only in hypoxic conditions is HIF-1α 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-1α is constitutively stabilized and active in the normal human retina. We investigated the cellular distribution of HIF-1α 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-1α 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-1α 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.
AB - 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-1α) is a transcription factor that is the master regulator of cellular adaptation to low oxygen tension. Only in hypoxic conditions is HIF-1α 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-1α is constitutively stabilized and active in the normal human retina. We investigated the cellular distribution of HIF-1α 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-1α 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-1α 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.
KW - Carbonic anhydrase
KW - Glucose transporter
KW - Hypoxia
KW - Hypoxia-inducible factor
KW - Retina
KW - VEGF
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U2 - 10.1369/jhc.2009.953786
DO - 10.1369/jhc.2009.953786
M3 - Article
C2 - 19901273
AN - SCOPUS:77649252795
SN - 0022-1554
VL - 58
SP - 247
EP - 254
JO - Journal of Histochemistry and Cytochemistry
JF - Journal of Histochemistry and Cytochemistry
IS - 3
ER -