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 journalArticle

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
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Retina
Facilitative Glucose Transport Proteins
Oxygen
Immunoblotting
Vascular Endothelial Growth Factor A
Staining and Labeling
Cell Hypoxia
Cell Nucleus
Ganglia
Energy Metabolism
Proteins
Transcription Factors
Immunohistochemistry
Light

Keywords

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

ASJC Scopus subject areas

  • Anatomy
  • Histology

Cite this

Hughes, J. M., Groot, A. J., Van Groep, P. D., Sersansie, R., Vooijs, M., Van Diest, P. J., ... Klaassen, I. (2010). Active HIF-1 in the normal human retina. Journal of Histochemistry and Cytochemistry, 58(3), 247-254. https://doi.org/10.1369/jhc.2009.953786

Active HIF-1 in the normal human retina. / Hughes, John M.; Groot, Arjan J.; Van Groep, Petra Der; Sersansie, René; Vooijs, Marc; Van Diest, Paul J.; Van Noorden, Cornelis J F; Schlingemann, Reinier O.; Klaassen, Ingeborg.

In: Journal of Histochemistry and Cytochemistry, Vol. 58, No. 3, 03.2010, p. 247-254.

Research output: Contribution to journalArticle

Hughes, JM, Groot, AJ, Van Groep, PD, Sersansie, R, Vooijs, M, Van Diest, PJ, Van Noorden, CJF, Schlingemann, RO & Klaassen, I 2010, 'Active HIF-1 in the normal human retina', Journal of Histochemistry and Cytochemistry, vol. 58, no. 3, pp. 247-254. https://doi.org/10.1369/jhc.2009.953786
Hughes JM, Groot AJ, Van Groep PD, Sersansie R, Vooijs M, Van Diest PJ et al. Active HIF-1 in the normal human retina. Journal of Histochemistry and Cytochemistry. 2010 Mar;58(3):247-254. https://doi.org/10.1369/jhc.2009.953786
Hughes, John M. ; Groot, Arjan J. ; Van Groep, Petra Der ; Sersansie, René ; Vooijs, Marc ; Van Diest, Paul J. ; Van Noorden, Cornelis J F ; Schlingemann, Reinier O. ; Klaassen, Ingeborg. / Active HIF-1 in the normal human retina. In: Journal of Histochemistry and Cytochemistry. 2010 ; Vol. 58, No. 3. pp. 247-254.
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