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V. Ramakrishnan, B.D. Kuppermann, V. Bhaskar, P. Wales, L.F. Hagemann, L. Marques, R.P. de Carvalho, C.G. Wong, R. Murray; F200, a Fab Derivative of M200 (Volociximab; Anti–A5ß1), Is a Potent Inhibitor of Angiogenesis in a Rabbit Model of Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2005;46(13):465.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate anti–α5ß1 antibodies in a rabbit model of sub–retinal choroidal neovascularization (CNV). Methods: Adult Dutch pigmented rabbits were implanted suprachroidally on Day 0 with either VEGF/bFGF Hydron® pellets or blank pellets. Animals were assessed by fundus photography (FP) and fluorescein angiography (FAs) at weeks 1,2,3,4, and 8. Clinical grading of FP and FA was performed by two masked graders on a 0–4 scale. Animals were sacrificed and enucleated at week 4 and week 8 for histology. In 2 separate experiments, F200 and M200 were assessed for (a) inhibition of sub–retinal CNV (b) efficacy of M200 administered I.V. (c) efficacy of a single dose of F200 and (d) efficacy of F200 administered as a treatment modality . Results: F200 and M200 are potent inhibitors of laser–induced CNV in the cynomolgus monkey model (ARVO 2003). In this report, F200 and M200 were tested in a novel rabbit model in which the development of CNV is progressive and appears primarily beneath the intact retina. We found that CNV develops in ∼40–70% of the eyes of animals implanted with the growth factor pellet, as assessed by FP and FA. F200 and M200 administered intravitreally or M200 administered I.V. at the time of pellet implantation (D0) and D15, suppressed the development of CNV to undetectable levels by week 4, unlike animals dosed with vehicle. F200 strongly inhibited the development of CNV in animals administered at D0 with a single high dose of drug, and this effect persisted for 8 weeks. Additionally, CNV was also significantly inhibited in animals treated with F200 one week after pellet implantation. No safety related issues were noted with M200 or F200. Conclusions: Anti–α5ß1 integrin antibodies M200 and F200 are potent inhibitors of in the rabbit model of sub–retinal CNV, showing significant activity when administered intravitreally or I.V. at the time of implant. Additionally, our data suggests that F200 inhibits CNV when administered in a therapeutic mode, and therefore these agents have potential for the treatment of age–related macular degeneration.
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