title: Regression of retinopathy by squalamine in a mouse model.
abstract: The goal of this study was to determine whether an antiangiogenic agent, squalamine, given late during the evolution of oxygen-induced retinopathy (OIR) in the mouse, could improve retinal neovascularization. OIR was induced in neonatal C57BL6 mice and the neonates were treated s.c. with squalamine doses begun at various times after OIR induction. A system of retinal whole mounts and assessment of neovascular nuclei extending beyond the inner limiting membrane from animals reared under room air or OIR conditions and killed periodically from d 12 to 21 were used to assess retinopathy in squalamine-treated and untreated animals. OIR evolved after 75% oxygen exposure in neonatal mice with florid retinal neovascularization developing by d 14. Squalamine (single dose, 25 mg/kg s.c.) given on d 15 or 16, but not d 17, substantially improved retinal neovascularization in the mouse model of OIR. There was improvement seen in the degree of blood vessel tuft formation, blood vessel tortuosity, and central vasoconstriction with squalamine treatment at d 15 or 16. Single-dose squalamine at d 12 was effective at reducing subsequent development of retinal neovascularization at doses as low as 1 mg/kg. Squalamine is a very active inhibitor of OIR in mouse neonates at doses as low as 1 mg/kg given once. Further, squalamine given late in the course of OIR improves retinopathy by inducing regression of retinal neovessels and abrogating invasion of new vessels beyond the inner-limiting membrane of the retina.
authors.affiliation: Department of Pediatrics, Georgetown University, Wshington, DC 20007, USA. higginsr@mail.nih.gov
authors.forename: Rosemary D
authors.initials: RD
authors.lastname: Higgins
authors.forename: Yun
authors.initials: Y
authors.lastname: Yan
authors.forename: Yixun
authors.initials: Y
authors.lastname: Geng
authors.forename: Michael
authors.initials: M
authors.lastname: Zasloff
authors.forename: Jon I
authors.initials: JI
authors.lastname: Williams
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002777:Cholestanols / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D012171:Retinal Vessels / Q000187:drug effects; D012178:Retinopathy of Prematurity / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D002777:Cholestanols; C079655:squalamine