Selective blockade of cytoskeletal actin remodeling reduces experimental choroidal neovascularization

Sergio Caballero, Ru Yang, Maria B. Grant, Brahim Chaqour

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

PURPOSE. The efficacy of the peptide Ac-EEED on reducing cell adhesion and proliferation in vitro and choroidal neovascularization (CNV) in vivo was examined. METHODS. The peptide chimera containing the Ac-EEED sequence was chemically linked to the N terminus of the XMTM delivery peptide from the Erns viral surface protein. Ac-EEED or scrambled control peptide (SCRAM) was added to cultures of vascular smooth muscle cells, pericytes, endothelial cells, and fibroblasts, and adhesion, growth, and matrix production was assessed. Ac-EEED or SCRAM was injected into the vitreous of mice undergoing laser rupture of Bruch's membrane to induce CNV and lesion volume, neovascularization and lesion fibrosis were assessed. RESULTS. Ac-EEED-induced changes in the morphology of the actin cytoskeleton by inhibiting polymerization of G-actin and disrupting the formation of stress fibers. Pretreatment with Ac-EEED resulted in endothelial cells becoming less responsive to the mitogenic and pro-adhesive effects of VEGF. Ac-EEED treatment in fibroblasts reduced TGF-β-induced fibrosis as assessed by decreased levels of connective tissue growth factor, cysteine-rich 61, collagen I (COL1A2), and collagen III (COL3A1). CNV lesion size and fibrosis were reduced in a concentration-dependent manner by up to 60%. CONCLUSIONS. In vitro studies showed that Ac-EEED affects a broad range of mechanical properties associated with cytoskeletal actin to reduce growth factor effects. The utilization of Ac-EEED in vivo may offer a novel therapeutic strategy by both suppressed neovessel growth and curtailing fibrosis typically associated with the involutional stage of CNV.

Original languageEnglish (US)
Pages (from-to)2490-2496
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number5
DOIs
StatePublished - Apr 1 2011

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ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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