Intraocular injection of an aptamer that binds PDGF-B: a potential treatment for proliferative retinopathies.

摘要: Platelet-derived growth factor-B (PDGF-B) has been implicated in the pathogenesis of proliferative retinopathies and other scarring disorders eye. In this study, we sought to test therapeutic potential an aptamer that selectively binds PDGF-B, ARC126, its PEGylated derivative, ARC127. Both ARC126 ARC127 blocked PDGF-B-induced proliferation cultured fibroblasts with IC50 4 nM. Pharmacokinetic studies rabbits showed similar peak vitreous concentrations approximately 110 µM after intravitreous injection 1 mg either or ARC127, but terminal half-life was longer for (98 versus 43 h). Efficacy tested rho/PDGF-B transgenic mice express PDGF-B photoreceptors develop severe retinopathy resulting retinal detachment. Compared eyes injected 20 µg scrambled which five six developed detachments (three total two partial), (no detachment one partial detachment), six) had significantly fewer detachments. They also a significant reduction epiretinal membrane formation. These data demonstrate single specifically is able reduce formation mice. striking effects aggressive model suggest should be considered treatment diseases implicated, including ischemic such as diabetic retinopathy, vitreoretinopathy (PVR), choroidal neovascularization. J. Cell. Physiol. 207: 407–412, 2006. © 2006 Wiley-Liss, Inc.