Redundant mechanisms for vascular growth factors in retinopathy of prematurity in vitro.
BACKGROUND
Current treatments for retinopathy of prematurity (ROP) targeting single vascular growth factors are ineffective in preventing neoangiogenesis.


METHODS
We investigated the redundant/compensatory mechanisms between vascular growth factors in ROP. Cultured retinal vascular endothelial cells under CoCl₂-induced hypoxia were transfected with recombinant adeno-associated virus type 2-vascular endothelial growth factor (VEGF) or pGIPZ-VEGF RNA interference to up- and downregulate VEGF expression, respectively. At 48 h after transfection, basic fibroblast growth factor (bFGF) and angiopoietin 1 (ANG1) gene expression as well as mitotic cycle changes were analyzed in the cells and correlated with the change in VEGF expression.


RESULTS
Compared with the normal control group 1, at 30 min, 12 h and 24 h, the expressions of VEGF, bFGF and ANG1 in the hypoxia control group 2 were significantly higher. In the highly expressing VEGF group (group 3), the expressions of bFGF and ANG1 were downregulated, while in the low-expressing VEGF group 4, the expressions of bFGF and ANG1 were significantly upregulated. In the bevacizumab treatment group 5, the expressions of VEGF, bFGF and ANG1 were similar to those in group 2, and the difference was not significant.


CONCLUSIONS
A compensatory mechanism (redundancy) exists between vascular growth factors in ROP. Such a phenomenon could partially explain why the inhibition of a single growth factor cannot effectively prevent the recurrence of neovascularization in ROP. A more effective strategy for treating ROP may be to inhibit VEGF and its redundant pathways.
Xiang
Nan
N
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Zhao
Min-Jian
MJ
Li
Xin-Yu
XY
Zheng
Hai-Hong
HH
Li
Gui-Gang
GG
Li
Bin
B
D000328:Adult; D042683:Angiopoietin-1 / Q000235:genetics*; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D010957:Plasmids; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015861:Retinal Neovascularization / Q000235:genetics; D012171:Retinal Vessels / Q000166:cytology; D012178:Retinopathy of Prematurity / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2