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Rosemary D. Higgins, Raymond J. Sanders, Yun Yan, Michael Zasloff, Jon I. Williams; Squalamine Improves Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1507-1512.
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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
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