Retinal neovascularization (RNV) is a characteristic pathological finding of
retinopathy of prematurity (ROP).
Cysteine-rich 61 [Cyr61, also known as CCN family member 1 (CCN1)] has been reported to mediate angiogenesis. The aim of the present study was to investigate the mechanisms of CCN1/Cyr61-
phosphoinositide 3-kinase (PI3K)/AKT signaling in ROP. The contribution of CCN1 to human umbilical vein endothelial cell (HUVEC) proliferation and apoptosis under hypoxic conditions was determined using a cell counting kit‑8 (CCK-8) and
Annexin V/
propidium iodide (PI) staining, respectively, as well as using
siRNA targeting CCN1 (CCN1
siRNA). The cells exposed to
hypoxia were also treated with the PI3K/AKT inhibitor,
LY294002. In addition, mouse pups with
oxygen-induced retinopathy (OIR) were administered an
intravitreal injection of CCN1
siRNA. RNV was assessed by
magnesium-activated
adenosine diphosphate-ase (
ADPase) staining. RT-qPCR, western blot analysis, immunofluorescence staining and immunohistochemistry were used to detect the distribution and expression of CCN1, PI3K and AKT. Exposure to
hypoxia increased the neovascularization clock hour scores (from 1.23±0.49 to 5.60±0.73, P<0.05) and the number of preretinal neovascular cells, as well as the
mRNA and
protein expression levels of CCN1, PI3K and AKT (all P<0.05). The injection of CCN1
siRNA decreased the neovascularization clock hour scores and the number of preretinal neovascular cells (1.53±0.72 vs. 4.76±1.04; 12.0±2.8 vs. 31.4±2.6, respectively, both P<0.05), as well as the
mRNA and
protein expression levels of CCN1, PI3K and AKT (
protein, -45.3, -22.5 and -28.4%;
mRNA, -43.7, -58.7 and -42.9%, respectively, all P<0.05) compared to the administration of scrambled
siRNA under hypoxic conditions. Treatment with
LY294002 decreased the
mRNA and
protein expression levels of CCN1 in the cells exposed to
hypoxia (both P<0.05). The administration of CCN1
siRNA resulted in less severe neovascularization in the eyes of the the mouse pups with OIR. Thus, out data suggest that CCN1 plays an important role in RNV in ROP, and may thus be a potential target for the prevention and treatment of ROP.