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.