Background
Retinopathy of prematurity (ROP), a major cause of significant visual morbidity and blindness in preterm infants, is closely related to pathological angiogenesis. The aim of the study is to evaluate the effect of a new 12‐aa peptide (named peptide CW‐703) from human insulin‐like growth factor‐2, against angiogenesis in ROP.
Methods
In order to evaluate the inhibitory effect of CW‐703 on the proliferation, migration, tube formation and apoptosis of human umbilical vein endothelial cells (ScienCell) in vitro, we used MTS assays, a modified Boyden chamber, Matrigel system and TUNEL assays. Effects in vivo were assayed using chorioallantoic membrane assays and oxygen‐induced retinopathy (OIR) models in mice. We also performed eletrophysiological and histologic examinations to evaluate the possible toxicity of the peptide. Real‐time PCR, ELISA and western blotting were used to elucidate the mechanism of CW‐703.
Results
CW‐703 inhibited angiogenesis in vitro by suppressing endothelial cell proliferation, migration and tube formation. CW‐703 also prevented angiogenesis in chicken chorioallantoic membrane assays and OIR assays in mice. No evident functional or morphologic abnormalities in neuroretina after CW‐703 injection were revealed in electrophysiological tests and histological examinations. Moreover, we elucidated that CW‐703 competed for binding to IGF‐1R and inhibited angiogenesis by inhibiting IGF‐1R/PI3K/AKT activation and downregulating vascular endothelial growth factor expression.
Conclusion
The novel peptide CW‐703 may act as an effective inhibitor of ocular pathologic angiogenesis, especially in treating ROP.