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Ian F. Pitha, Michael B. Sporn, Rajendra S. Apte; Inhibition of Choroidal Neovascularization by the Synthetic Oleanane Triterpenoid CDDO-Im. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4879.
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Synthetic oleanane triterpenoids (SO) are natural plant product derivatives with potent anti-inflammatory and anti-oxidant activity in diverse in vitro and in vivo settings. Recent evidence showed anti-angiogenic activity of these compounds. These studies test the ability of the SO, CDDO-Im to inhibit pathologic angiogenesis in a preclinical model of choroidal neovascularization (CNV).
6 week old C57Bl/6J, female mice were treated with the SO CDDO-Im or vehicle control by daily, intraperitoneal injection. On day 3 of treatment, CNV was induced by rupture of Bruchs membrane using a krypton red laser. Treatment was continued until day 11. CNV was then visualized using fluorescein angiography and threshold CNV area was quantified using digital imaging software. Average CNV area and standard error were calculated. Significance was determined by Student's t-test analysis.
CDDO-Im inhibited CNV formation in a dosage dependent manner. Average CNV area in control mice was (8424±870 threshhold units (tu)). Mice treated with 3 micromole/kg mouse weight CDDO-Im had significantly reduced CNV area (4284±810 tu, p=0.0011) while mice treated with 0.3 micrograms/kg (5807±885 tu, p=0.056) did not display significant reduction in CNV.
The SO, CDDO-Im inhibits pathologic angiogenesis in a preclinical model of CNV formation. Further studies are required to determine the molecular mechanisms and clinical potential of SO in treatment of pathologic CNV.
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