Circulating endothelial progenitor cells are reduced in rat oxygen-induced retinopathy despite a retinal SDF-1/CXCR4 and VEGF proangiogenic response

Life Sci. 2012 Sep 17;91(7-8):264-70. doi: 10.1016/j.lfs.2012.07.019. Epub 2012 Jul 31.

Abstract

Aims: The purpose of this study is to investigate circulating endothelial progenitor cells (EPCs) and the signaling pathways involved in their recruitment in the ischemic retina of the 50/10 rat model of oxygen-induced retinopathy (OIR).

Main methods: Within 12h after birth, litters of Sprague-Dawley rats and their mothers were exposed to alternating oxygen concentrations, followed by a room air exposition, to induce OIR. Retinopathy was quantified by ADPase stain in flat-mounted retinas and pre-ILM nuclei count in retinal sections. Semiquantitative real-time PCR and immunofluorescence were assessed in retinas to study stromal cell-derived factor 1 (SDF-1), its receptor CXCR4 and vascular endothelial growth factor (VEGF) expression. Circulating EPCs were evaluated by flow cytometry in peripheral blood.

Key findings: Our results showed increased immunolabelling of SDF-1 in endothelial cells and strong expression of CXCR4 in Müller cells in OIR retinas as compared to control retinas. We found increased levels of CXCR4 and VEGF mRNA in OIR retinas, especially during the vascular attenuation stage. The number of circulating EPCs was decreased in OIR rats as compared to control rats.

Significance: The decrease in circulating EPCs could be implied in vessel growth arrest during normal retinal development in OIR rats, while pro-angionenic signals released by Müller cells in the hypoxic retina could drive pathological neovascularization in the ischemic retina. These data warrant further studies to investigate new therapeutic approaches for ROP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / pathology
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / physiology*
  • Endothelial Cells / cytology*
  • Flow Cytometry
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry
  • Neovascularization, Pathologic*
  • Oxygen / administration & dosage*
  • Oxygen / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / physiology*
  • Retinal Diseases / etiology*
  • Retinal Diseases / metabolism
  • Retinal Diseases / physiopathology
  • Retinal Vessels / metabolism
  • Retinal Vessels / physiopathology*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / physiology*

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Glial Fibrillary Acidic Protein
  • Receptors, CXCR4
  • Vascular Endothelial Growth Factor A
  • Oxygen