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Squalamine Improves Retinal Neovascularization

¹ From the Department of Pediatrics, Division of Neonatology, Georgetown University Medical Center, Washington, DC; the ² Department of Pediatrics, Neonatal Program, New York University Medical Center, New York; and ³ Magainin Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania.

PURPOSE. Modalities for inhibiting neovascularization may be one avenue to the development of effective therapies for retinopathy. The effect of squalamine, an antiangiogenic amino sterol, on oxygen-induced retinopathy (OIR) was assessed in a mouse model.

METHODS. OIR was induced in C57BL6 mice by a 5-day exposure to 75% oxygen from postnatal day (P)7 through P12. Squalamine (25 mg/kg, subcutaneous)-treated animals received either daily doses for five days from P12 to P16 or one dose just after removal from oxygen on P12. Each set of animals was killed at P17 to P21. Retinopathy was assessed with a retinopathy scoring system evaluation of retinal wholemounts and by quantification of neovascular nuclei on retinal sections.

RESULTS. Animals receiving 5 days of squalamine after a 5-day exposure to oxygen had total retinopathy scores (expressed as median score with 25th and 75th quartiles in parentheses) of 4(3, 5) versus oxygen-only–reared animals with scores of 8(7, 9; P < 0.001). Animals reared in room air and animals exposed to squalamine only had similar retinopathy scores: 1(1, 2) and 1(0, 2). Oxygen-reared animals receiving single-dose squalamine also showed improvement, with a median retinopathy score of 4(4, 6.75) versus oxygen-only–reared animals with median retinopathy score of 9(7, 10; P < 0.001). There was a decreased number of neovascular nuclei extending beyond the inner limiting membrane on retinal sections in animals treated with 5 days (P < 0.01) and 1 day (P < 0.001) of squalamine.

CONCLUSIONS. Squalamine significantly improved retinopathy and may be a novel agent for effective treatment of ocular neovascularization.

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