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S. G. Emeigh Hart, J. D. Akula, H.-L. Hung, M. P. McLane, A. L. Asturias, A. R. Dagi, R. M. Hansen, M. E. Martinez-Perez, A. B. Fulton; Squalamine Improves Vascular and Neural Outcomes in Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4053.
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Retinopathy of prematurity (ROP) is characterized by both abnormal retinal vasculature (increased vessel tortuosity and curvature) and dysfunction of the neural retina. This study examined the affects of squalamine (an antiangiogenic aminosterol) on retinal vasculature morphology and on the function and structure of the neural retina in a rat model of ROP.
Retinopathy was induced by exposing rats to continuous 75% oxygen from postnatal day (P) 7-14. From P14-P28, rats were administered 10 mg/kg squalamine (n=12) or vehicle alone (n=12) IP. Serial electroretinographic (ERG) tests were used to assess rod photoreceptor and post-receptor function at P20±1, P30±1, and P60±1. Digital fundus photographs were obtained in the same sessions, and Retinal Image multiScale Analysis (RISA), software used to calculate the integrated curvature (IC) of the retinal arterioles and venules. Eyes were collected from a set of littermates on P14, P20, and P30 for light microscopic histologic assessment. Significant changes in each ERG/RISA parameter were detected by two-factor (treatment; age) analysis of variance.
At P20 and P30, both rod photoreceptor and post-receptor sensitivities were significantly (P≤0.05) higher in squalamine treated rats. Rod photoreceptor sensitivities were also markedly higher in squalamine treated rats on P60. IC was significantly higher for arterioles than venules in the ROP model; arteriolar IC was significantly lowered by squalamine, especially on P20. Histologically, the quantity, complexity, and depth of penetration of the inner-retinal vasculature were notably reduced by squalamine on P20; these differences were less apparent on P30. Body weight was unchanged by squalamine
These results indicate that squalamine improves outcomes for both the retinal vasculature and neural retina. The improvement is especially marked at young ages, and thus may foster more normal retinal development in ROP.
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