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R. Lima e Silva, S. Kachi, N. H. Khu, S. Hackett, D. P. Bingaman, C. Romano, P. A. Campochiaro; Periocular or Intraocular Injection of AL-39324, a Novel Kinase Inhibitor That Blocks VEGF Receptors, Suppresses Choroidal Neovascularization (CNV) in Pigs. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1471.
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© ARVO (1962-2015); The Authors (2016-present)
The aim of this study was to assess the effect of AL-39324 on CNV in a human-sized eye.
Four week-old female Yorkshire pigs had laser-induced rupture of Bruch’s membrane in each eye followed by 3 treatment paradigms: 1) periocular injection of 500µL containing 0, 5 or 10% AL-39324, 2) intraocular injection of 500µL containing 0, 0.3, or 3%, or 3) 100µL l containing 0.06 and 0.3%. The area of CNV at rupture sites was measured 10 days after injections.
The area of CNV at Bruch’s membrane rupture sites was significantly less in eyes given a periocular injection of 5 or 10% AL-39324 (↓83% and 79%, respectively) compared to eyes injected with vehicle (0.027±0.008 and 0.021±0.003 versus 0.16±0.02 and 0.10±0.016 n=12, p=0.0035 and p=0.0015 by two-tail t-test). Intraocular injections of 0.5 ml of 0.3% or 3% (↓64% and 77%, respectively) (0.036±0.0112 and 0.023±0.0105 versus 0.100±0.0172, n=12, p=0.01 and p=0.0038) or 0.1 ml of 0.06 or 0.3 % of AL-39324 (↓58% and 75%, respectively) (0.046±0.0068 and 0.028±0.0027 versus 0.11±0.0149, n=12, p=0.02 and p=0.00001) also suppressed CNV compared to vehicle.
AL-39324 strongly suppresses CNV when given by periocular or intraocular injection in a human-sized eye and therefore is a viable candidate for the treatment of exudative AMD.
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