Active HIF-1 in the Normal Human Retina

• Published in: The journal of histochemistry and cytochemistry Vol. 58; no. 3; pp. 247 - 254
• Main Authors: Hughes, John M, Groot, Arjan J, van der Groep, Petra, Sersansie, Rene, Vooijs, Marc, van Diest, Paul J, Van Noorden, Cornelis J.F, Schlingemann, Reinier O, Klaassen, Ingeborg
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA Histochemical Soc 01.03.2010; SAGE Publications; Histochemical Society
• Subjects: Adult; Aged; Animals; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunoblotting; Immunohistochemistry; Male; Middle Aged; Rats; Rats, Wistar; Retina - metabolism; Retina - ultrastructure; carbonic anhydrase; hypoxia; hypoxia-inducible factor; glucose transporter; retina; VEGF
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1369/jhc.2009.953786

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.