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G.J. Coleman, A. Boutaud, T.A. Gardiner, A.W. Stitt; AngiocolTM, a type IV collagen fragment, modulates retinal angiogenesis in vitro. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1911.
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© ARVO (1962-2015); The Authors (2016-present)
Abstract: : Purpose:A number of endogenous collagen fragments have been identified to possess anti–angiogenic activity. One such collagen molecule termed AngiocolTM (derived from the collagen 2(IV) NC1 domain) has previously been shown to effectively inhibit macrovascular endothelial cell proliferation both in vivo and in vitro via interaction with the alpha v beta 3 integrin. The present study has examined the potential of AngiocolTM to modulate angiogenic activity in retinal microvascular endothelial cells and represents the first stage in evaluation of this clinically relevant agent for the treatment of retinal neovascularisation. Methods:To evaluate AngiocolTM effects upon retinal microvascular endothelial cells (RMEC’s) a concentration range of the drug was used in an apoptosis assay whereby cell death was calculated using manual cell counts via phase contrast microscopy. Similarly, RMEC’s were treated with varying concentrations of AngiocolTM to evaluate the drug effect upon endothelial cell attachment to gelatin substrate. To investigate the effect of AngiocolTM upon retinal angiogenesis, a novel 3–D assay was employed and the number of RMEC angiogenic sprouts arising form pre–existing vascular tubes were quantified and compared against non drug–infused controls. Results:AngiocolTM significantly increased RMEC death after comparison with non–treated controls in a dose–dependent fashion (p<0.05). AngiocolTM did not significantly alter the attachment of retinal endothelial cells to gelatin matrices. This peptide fragment demonstrated a potent anti–angiogenic effect by significantly reducing the number of RMEC angiogenic sprouts penetrating the secondary layer of Matrigel in comparison with controls (p<0.05). Conclusions:AngiocolTM appears to modulate key aspects of retinal angiogenesis. Further studies are ongoing to evaluate this drug as a potential candidate for the treatment of retinal neovascularisation.
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