Higgins R D, Sanders R J, Yan Y, Zasloff M, Williams J I
Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA.
Invest Ophthalmol Vis Sci. 2000 May;41(6):1507-12.
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.
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.
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.
Squalamine significantly improved retinopathy and may be a novel agent for effective treatment of ocular neovascularization.
抑制新生血管形成的方法可能是开发视网膜病变有效治疗方法的一条途径。在小鼠模型中评估了一种抗血管生成氨基甾醇角鲨胺对氧诱导性视网膜病变（OIR）的影响。
通过从出生后第（P）7天至P12天暴露于75%氧气5天，在C57BL6小鼠中诱导OIR。角鲨胺（25mg/kg，皮下注射）处理的动物从P12至P16接受为期五天的每日剂量，或在P12从氧气环境中取出后立即接受一剂。每组动物在P17至P21处死。通过视网膜平铺片的视网膜病变评分系统评估和视网膜切片上新血管细胞核的定量来评估视网膜病变。
在暴露于氧气5天后接受5天角鲨胺治疗的动物，其总视网膜病变评分（表示为中位数评分，括号内为第25和第75四分位数）为4（3，5），而仅饲养在氧气环境中的动物评分为8（7，9；P<0.001）。饲养在室内空气中的动物和仅暴露于角鲨胺的动物具有相似的视网膜病变评分：1（1，2）和1（0，2）。接受单剂量角鲨胺的氧气饲养动物也显示出改善，其视网膜病变中位数评分为4（4，6.75），而仅饲养在氧气环境中的动物视网膜病变中位数评分为9（7，10；P<0.001）。在接受5天（P<0.01）和1天（P<0.001）角鲨胺治疗的动物中，视网膜切片上延伸至内界膜以外的新血管细胞核数量减少。
角鲨胺显著改善了视网膜病变，可能是有效治疗眼部新生血管形成的新型药物。
