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C. V. Regatieri, J. L. Dreyfuss, M. A. Lima, E. H. Farias, A. S. Brito, S. F. Chavante, H. B. Nader, M. E. Farah; Intravitreous Heparin-Like Glycosaminoglycan Isolated From a Marine Shrimp Induces Regression of Experimental Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3500.
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It has been shown that a heparin-like glycosaminoglycan obtained from shrimp cephalotorax (Litopenaeus vannamei) is capable to modulate inflammatory responses without interfering on hemostasis. Besides it reduced bleeding potential and anticoagulant activity in vitro, the shrimp heparin-like compound is able to reduce the activity of matrix metalloproteinases, enzymes involved on basal membrane degradation during the angiogenesis process. Thus the objective of this study was to evaluate the effects of this new compound on a laser-induced choroidal neovascularization (CNV) in pigmented Zucker rats and verify the cytotoxicity of this compound in retina pigmented epithelial cells (ARPE-19).
Induction of CNV was performed using argon laser. At the end of laser session, saline or heparin-like glycosaminoglycan were injected intravitreously. The animals were divided into 4 groups (laser, and laser with 0.09, 0.9 and 9 µg/mL of heparin-like glycosaminoglycan). After three weeks, the eyes were enucleated and immunofluorescence was performed (flatmount) using anti-von Willebrand factor, a marker for endothelial cells. The cytotoxicity of heparin-like glycosaminoglycan was evaluated by MTT test in ARPE-19 cell culture.
Immunofluorescence analysis showed significant reduction in CNV lesion area of all groups treated with heparin-like glycosaminoglycan. The regression observed was 28%, 53% and 41% in 0.09, 0.9 and 9 µg/mL treated groups, respectively (P<0.0001). No cytotoxic effect was detected in ARPE-19 cell culture.
Intravitreal heparin-like glycosaminoglycan from a marine shrimp significantly reduces the CNV lesion area. The optimal dosage to reduce angiogenesis was 0.9 µg/mL and it was non-toxic to the retina pigmented epithelial cells. These results demonstrated a new useful antiangiogenic compound that can be used as a therapy to control choroidal neovascularization.
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