VEGF-A, VEGFR-1, VEGFR-2 and Tie2 levels in plasma of premature infants: relationship to retinopathy of prematurity.
OBJECTIVE
To study prospectively the 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 23-32 weeks were obtained between 5 days and 15 weeks after birth. 42 infants had no ROP, two had stage 1, nine stage 2 and 10 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. The time course of concentrations plotted by kernel smoothing in infants with and without ROP were compared and a paired subgroup with analysis of variance was analysed.


RESULTS
ROP patients had raised plasma levels of sVEGFR-2 and sTie2 compared with 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).


CONCLUSIONS
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 increases have yet to be confirmed as predictive values for ROP.
Pieh
C
C
Department of Ophthalmology, University Hospital Freiburg, Freiburg, Germany. christina.pieh@uniklinik-freiburg.de
Agostini
H
H
Buschbeck
C
C
Krüger
M
M
Schulte-Mönting
J
J
Zirrgiebel
U
U
Drevs
J
J
Lagrèze
W A
WA
D000704:Analysis of Variance; D018450:Disease Progression; D005865:Gestational Age; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D011446:Prospective Studies; D042787:Receptor, TIE-2 / Q000097:blood*; D012178:Retinopathy of Prematurity / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2