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MH Criswell, TA Ciulla, RP Danis, JI Williams, MP McLane, KJ Holroyd; Squalamine Lactate Inhibits Choroidal Neovascular Membrane (CNVM) Formation in a Rat Laser-Trauma Model . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1264.
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Purpose: Squalamine is an aminosterol, originally isolated from the tissues of the dogfish shark, which exhibits low systemic toxicity and which recently demonstrated antiangiogenic effects in a mouse model of retinopathy of prematurity (Higgins, R.D., et al., Invest Ophthalmol Vis Sci. 2000; 41:1507). Here we characterize the inhibitory effects of squalamine on CNVM formation in a rat laser-trauma CNVM model. Methods: A series of 8 concentrically-arranged lesion sites was placed bilaterally around the optic disks of 20 Brown Norway rats using a krypton red laser (Coherent: 647 nm, 0.05 sec, 150 mW, 50 µm). Following lesion induction, 10 rats immediately began to receive a series of systemic intraperitoneal injections of squalamine (dosage: 5mg/kg/injection, b.i.d.) for 9 days out of the 28 day experimental period. The remaining 10 control rats received similar injections that contained only D5W. Follow up fundus, fluorescein angiography (FA), and tissue histology examinations were conducted. Results: Fundus and FA yielded only subtle indications of differences between the two groups. Histologic analysis of lesion sites revealed partial, but significant (p < 0.001) inhibition of CNVM mean thickness of the squalamine-treated group (47 ± 11 mm), as compared to the mean thickness (63 ± 14 mm) of the control group. Conceivably, the initial time for systemic squalamine levels to develop versus the fast and aggressive CNVM development characteristics of this particular animal model may have partially masked the overall efficacy of squalamine. Conclusion: Systemically administered squalamine lactate partially inhibits neovascular development in this CNVM rat model. In conjunction with other existing and developing therapies, squalamine may have a potential role in the treatment of human CNVM formation.
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