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

Hideo Akiyama, Shu Kachi, Raquel Lima E Silva, Naoyasu Umeda, Sean F. Hackett, Dilara McCauley, Thomas McCauley, Anna Zoltoski, David M. Epstein, Peter A. Campochiaro

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish (US)
Pages (from-to)407-412
Number of pages6
JournalJournal of Cellular Physiology
Volume207
Issue number2
DOIs
StatePublished - May 1 2006

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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