Expression of IGFBP-6 in a proliferative vitreoretinopathy rat model and its effects on retinal pigment epithelial cell proliferation and migration

Abstract

AIM: To investigate the expression of insulin-like growth factor binding protein-6 (IGFBP-6) in a proliferative vitreoretinopathy (PVR) model and its effects on proliferation and migration in retinal pigment epithelial (RPE) cells.METHODS: A PVR Wistar rat model was established by the intravitreal injection of RPE-J cells combined with platelet-rich plasma (PRP). The expression levels of IGFBP-6 were tested by ELISA. ARPE-19 cell proliferation was evaluated by the MTS method, and cell migration was evaluated by wound healing assays.RESULTS: The success rate of the PVR model was 89.3% (25/28). IGFBP-6 was expressed at higher levels in the vitreous, serum and retina of rats experiencing advanced PVR (grade 3) than in the control group (vitreous:152.80±15.08ng/mL vs 105.44±24.81ng/mL, P>0.05; serum:93.48±9.27ng/mL vs 80.59±5.20ng/mL, P<0.05; retina:3.02±0.38ng/mg vs 2.05±0.53ng/mg, P<0.05). In vitro, IGFBP-6 (500ng/mL) inhibited the IGF-II (50ng/mL) induced ARPE-19 cell proliferation (OD value at 24h:from 1.38±0.05 to 1.30±0.02; 48h:from 1.44±0.06 to 1.35±0.05). However, it did not affect basal or VEGF-, TGF-β- and PDGF-induced cell proliferation. IGFBP-6 (500ng/mL) reduced the IGF-II (50ng/mL)-induced would healing rate [24h:from (43.91±3.85)% to (29.76±2.49)%; 48 h:from (66.09±1.67)% to (59.88±3.43)%].CONCLUSION: Concentrations of IGFBP-6 increased in the vitreous, serum, and retinas only in advanced PVR in vivo. IGFBP-6 also inhibited IGF-II-induced cell proliferation in a not dose or time dependent manner and migration. IGFBP-6 participates in the development of PVR and might play a protective role in PVR.

Keywords

• insulin-like growth factor binding protein-6
• proliferative vitreoretinopathy
• retinal pigment epithelial cells
• retinal pigment epithelial cells