Active HIF-1 in the normal human retina

John M. Hughes, Arjan J. Groot, Petra Der Van Groep, René Sersansie, Marc Vooijs, Paul J. Van Diest, Cornelis J.F. Van Noorden, Reinier O. Schlingemann, Ingeborg Klaassen

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)247-254
Number of pages8
JournalJournal of Histochemistry and Cytochemistry
Volume58
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Carbonic anhydrase
  • Glucose transporter
  • Hypoxia
  • Hypoxia-inducible factor
  • Retina
  • VEGF

ASJC Scopus subject areas

  • Anatomy
  • Histology

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