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VEGF-A, VEGFR-1, VEGFR-2 and Tie2 levels in plasma of premature infants: Relationship to retinopathy of prematurity
  1. Christina Pieh (christina.pieh{at},
  2. Hansjürgen Agostini (hansjuergen.agostini{at},
  3. Christiane Buschbeck (c.buschbeck{at},
  4. Marcus Krüger (marcus.krueger{at},
  5. Jürgen Schulte-Mönting (jsm{at},
  6. Ute Zirrgiebel (u.zirrgiebel{at},
  7. Joachim Drevs (drevs{at},
  8. Wolf Alexander Lagrèze (mail{at}
  1. University of Freiburg, Ophthalmology, Germany
  2. University of Freiburg, Ophthalmology, Germany
  3. University of Freiburg, Ophthalmology, Germany
  4. University of Freiburg, Pediatrics, Germany
  5. University of Freiburg, Medical Biometry and Statistics, Germany
  6. Clinical Biomarker Analysis, ProQinase GmbH, Germany
  7. University of Freiburg, Cancer Biology, Germany
  8. University of Freiburg, Ophthalmology, Germany


    Aim: To prospectively study plasma levels of vascular endothelial growth factor (VEGF-A), its soluble receptors sVEGFR-1, sVEGFR-2, and soluble Tie2 in premature infants. To identify their changes related to the onset of retinopathy of prematurity (ROP).

    Methods: Blood samples of 63 preterm infants born at a postmenstrual age (PMA) of 23 to 32 weeks were obtained between five days and 15 weeks after birth. 42 infants had no ROP, two had stage 1, nine stage 2 and ten stage 3. Of these, four infants were treated with retinal photocoagulation. VEGF-A, sVEGFR-1, sVEGFR-2, and sTie2 were measured in the plasma with a sandwich-enzyme-immunoassay using factor-specific monoclonal mouse antibodies. We compared the time course of concentrations plotted by kernel smoothing in infants with and without ROP and analysed a paired subgroup with ANOVA.

    Results: ROP patients had raised plasma levels of sVEGFR-2 and sTie2 compared to premature infants without ROP. VEGF-A and sVEGFR-1 levels were similar in both groups. Analysis of a subgroup with pairs of measurements, one before 32 weeks and one after 36 weeks, showed a significant increase in sTie2 after 36 weeks of PMA independent of ROP (p=0.03).

    Conclusion: This is the first study to measure plasma levels of angiogenic factors in ROP. Similar VEGF-A plasma levels in infants with and without ROP suggest that pathogenic retinal angiogenesis in ROP is mainly driven by local VEGF-A synthesis. Elevated plasma levels in active ROP were observed for sVEGFR-2 and sTie2. These rises have yet to be confirmed as predictive values for ROP.

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