RESUMEN
PURPOSE: The purpose of this study was to measure the anti-angiogenic effect of N-desulfated Re-N-acetylated, a chemically modified heparin (mHep). METHODS: In vitro assays (cell tube formation, viability, proliferation, and migration) with endothelial cells were performed after 24 h of treatment with mHep at 10, 100, and 1000 ng/mL or saline. In vivo tests were performed after laser-induced choroidal neovascularization (CNV) in rats, followed by an intravitreal injection (5 µL) of mHep (10, 100, 1000 ng/mL) or balanced salt solution. Immunofluorescence analysis of the CNV was performed after 14 days. RESULTS: mHep produced a statistically significant reduction in cell proliferation, tube formation, and migration, without cell viability changes when compared to saline. Mean measures of CNV area were 54.84 × 106 pixels/mm (± 12.41 × 106), 58.77 × 106 pixels/mm (± 17.52 × 106), and 59.42 × 106 pixels/mm (± 17.33 × 106) in groups 100, 1000, and 10,000 ng/mL, respectively, while in the control group, mean area was 72.23 × 106 (± 16.51 × 106). The P value was 0.0065. Perimeter analysis also demonstrated statistical significance (P = 0.0235) with the mean measure of 93.55 × 104, 94.23 × 104, and 102 × 104 in the 100 ng/mL, 1000 ng/mL, and control groups, respectively. CONCLUSIONS: These results suggest that mHep N-DRN is a potent anti-angiogenic, anti-proliferative, and anti-migratory compound with negligible anticoagulant or hemorrhagic action and no cytotoxicity for retina cells. This compound may serve as a candidate for treating choroidal neovascularization.
