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N. Jo, C. Mailhos, K. Nishijima, M. Ju, E. Cheung, G.S. Robinson, A.P. Adamis, D.T. Shima; Mural Cell Loss Following Inhibition of PDGF Signaling Enhances the Effect of Anti–VEGF Therapy on Corneal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2005;46(13):468.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To test whether targeting mural cells (MCs) with a specific PDGF–B signaling inhibitor enhances the effect of anti–VEGF reagents at inhibiting corneal neovascularization (CoNV). Methods: CoNV was induced by removal of the corneal epithelia. Mice were treated with either PDGF–B signaling inhibitors, anti–VEGF aptamer, or both in combination at various time points post–injury. Corneal NV was analyzed using concanavalin A lectin staining to mark the endothelium, smooth muscle actin antibody staining to mark mural cells (MCs), and by electron microscopy for morphological analysis. Results: Inhibition of PDGF–B signaling blocked MC recruitment to newly growing vessels and caused MC detachment from recently established neo–vessels. However, interfering with PDGF–B signaling alone resulted in no significant inhibition of vessel growth. In contrast, blocking VEGF signaling using Macugen TM, an anti–VEGF165 aptamer, was effective at preventing corneal NV, but less effective at regressing established corneal vessels. Macugen efficacy over time, however, was greatly improved by using it in combination with PDGF–blocking reagents capable of disrupting the endothelial/MC interaction. Conclusions: We have found that MC loss following inhibition of PDGF–B signaling enhances the effect of anti–VEGF therapy on corneal NV. Thus, combination therapy using both VEGF and PDGF–B inhibitors could be a more effective treatment for patients with advanced ocular NV.
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