Anti-angiogenesis effect of AMD3100 in oxygen-induced retinopathy mice

Abstract

To observe the inhibition of neovascularisation in the oxygen-induced retinopathy (OIR) mice by a stromal cell-derived factor 1 (SDF-1) antagonist. Experimental study. Fifty-eight 7-day-old C57BL/6 mice were divided into 3 groups randomly, the control group (n = 17), the test group (n = 17) and the medication group (n = 24). According to the dosage of AMD3100, the medication group (n = 24) were divided into low dose group, high dose group, low dose control group, and high dose control group (each group n = 6). Each group (19-day-old) was sacrificed to perform ADPase staining, paraffin sections and immunohistochemical staining (anti-VEGF and anti-SDF-1). The average positive staining area percentage (APSAP) was measured as the outcomes and processed with the Students' t-test. Real-time PCR showed expression of both VEGF mRNA (0.080 ± 0.022 vs. 0.123 ± 0.032) and SDF-1 mRNA (0.731 ± 0.099 vs.0.544 ± 0.108) in retinas from the control group and test group, respectively. The expression of these factors in the test group was significantly higher (t = 2.488, P = 0.038;t = 2.864, P = 0.021). The number of neovascular endothelial nuclear that broke through the retinal internal limiting membrane in the paraffin section in the high dose group and the low dose group was significantly less than that in the self-control group (t = -9.507, P = 0.000; t = -10.761, P = 0.000). The appearance of ADPase staining sections in the medication group was more similar to the simple control group than that of the test group. Immunohistochemical staining sections showed that VEGF and SDF-1 expressed in neuroepithelial cells in each group. APSAP in the high dose group and the low dose group was significantly lower than that in the self-control group (VEGF: t = -7.249, P = 0.000; t = -9.02, P = 0.000; SDF-1: t = -5.246, P = 0.000; t = -5.216, P = 0.000). These results indicate that AMD3100 block the SDF-1 receptor to reduce the effect of SDF-1, decrease the production of VEGF protein and inhibite neovascularization.