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.