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T.L. Yanovitch, R.M. Siatkowski, R. Archer, J.D. Ash; The Effect of D–Penicillamine on a Murine Model of Oxygen Induced Retinopathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1758.
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Previous studies have suggested that the chelating agent D–Penicillamine (DPA) effectively prevents retinopathy of prematurity in premature infants. The long–term goal of our study is to determine the mechanism of inhibition. The purpose of this study was to determine the safety and efficacy of DPA in preventing neovascularization in the mouse model of oxygen–induced retinopathy.
Litters of mice at post–natal day 7 (P7) were placed with their mothers in an animal chamber in which the environmental oxygen concentration was maintained at 75% oxygen for 6 days then returned to room air for 4 days to induce retinal neovascularization. The treatment group (n=8) received subcutaneous injections of DPA at a dose of 300mg/kg/day for 3 days beginning at P7 and then 50mg/kg/day from P7 to P17. The control group (n=8) received no treatment. At post–natal day 17, the eyes were enucleated and fixed. The retinas were dissected, stained with lectin and flat mounted. Neovascular glomeruli and tubules were then counted in both groups via confocal microscopy. The study was repeated using 2x and 4x the original dosage of DPA.
DPA was well tolerated with no observable side effects. At the lower doses there was no difference in neovascularization between the control and treatment groups. Results are pending for the higher dosage groups.
The chelating agent DPA was well tolerated. Low dose DPA does not prevent neovascularization in oxygen–induced retinopathy. Once we have found the dose of DPA that inhibits neovascularization in mice, we will use this model to study the mechanism.
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