Intravitreal Stanniocalcin-1 enhances new blood vessel growth in a rat model of laser-induced choroidal neovascularization

Abstract

Purpose : We previously observed that stanniocalcin-1 (STC-1) reduced photoreceptor degeneration and oxidative stress in two different rodent models of inherited retinal degeneration. Interestingly, several investigators recently demonstrated upregulation of STC-1 expression in specific cancers and an association with tumor angiogenesis. The role of STC-1 in ocular neovascularization has not been previously investigated. Herein, we studied the effect of intravitreal injection of STC-1 in relation to vascular endothelial growth factor (VEGF) and its receptor expression in a rat model of laser-induced choroidal neovascularization (CNV).

Methods : CNV was induced by laser photocoagulation in both eyes of Brown Norway rats. The right eye received a 5 µl intravitreal injection of 0.5 µg/µL STC-1. The left eye received an intravitreal injection of balanced salt solution. Two weeks after laser photocoagulation, fundus autofluorescence, infrared, and blue reflectance images; fundus fluorescein angiography (FFA); and spectral domain optical coherence tomography (OCT) were recorded using the Heidelberg Spectralis HRA+OCT. The area of CNV fluorescein leakage and the volume of the CNV lesions were measured by FFA and OCT, respectively. The area of CNV was also quantified by RPE-choroid-sclera flatmounts perfused with FITC–dextran. The expressions of STC-1, VEGF, and VEGF receptor-2 (VEGFR-2) in the CNV lesions were evaluated by immunofluorescence staining of the flatmounts. Statistical analysis was performed with one-way ANOVA or two-tailed t-tests.

Results : The size of the CNV lesions in the STC-1 treatment group was significantly increased compared with the control group 2 weeks after laser photocoagulation. The mean volume of the CNV lesions increased by 59% as measured by OCT (P<0.05, n=23). The mean area of the CNV lesions increased by 74% as measured by flatmounts perfused with FITC–dextran (P<0.05, n=12). STC-1, VEGF, and VEGFR-2 were highly expressed in the CNV lesions by immunofluorescence staining of the flatmounts.

Conclusions : STC-1, VEGF, and VEGFR-2 are highly expressed in laser-induced CNV in the rodent model. Intravitreal administration of STC-1 appears to enhance new blood vessel growth after laser injury in this experimental CNV model. STC-1 may enhance the development of CNV via increased VEGF expression or direct activation of VEGFR-2.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.