April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Selective Blockade of Cytoskeletal Remodeling Reduces Experimental Choroidal Neovascularization
Author Affiliations & Notes
  • S. Caballero, Jr.
    Pharmacology/Therapeutics, University of Florida, Gainesville, Florida
  • B. Chaqour
    Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York
  • R. Yang
    Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York
  • M. B. Grant
    Pharmacology/Therapeutics, University of Florida, Gainesville, Florida
  • Footnotes
    Commercial Relationships  S. Caballero, Jr., None; B. Chaqour, None; R. Yang, None; M.B. Grant, None.
  • Footnotes
    Support  NIH Grants EY012601 and EY007739
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3358. doi:
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    • Get Citation

      S. Caballero, Jr., B. Chaqour, R. Yang, M. B. Grant; Selective Blockade of Cytoskeletal Remodeling Reduces Experimental Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3358.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Endothelial cell migration is crucial to neovascularization, and the ability to migrate depends on cytoskeletal remodeling. We designed a fusion peptide chimera (EED) composed of an N-terminal acetylated nanopeptide that blocks reversibly actin and actin-binding protein interactions, and the N-terminus of the XMTM delivery peptide from the Erns viral surface protein to efficiently translocate attached cargo molecules into cells and tissues. We examined the ability of EED peptide to interfere with cytoskeletal remodeling in vitro, and its potential inhibitory effects on choroidal neovascularization (CNV) using the mouse model of laser rupture to Bruch’s membrane.

Methods: : Vascular smooth muscle cells were incubated with EED peptide (5 ng/uL) for various periods of times and stained with rhodamine-labeled phalloidin. Adult female C57BL6/J mice were subjected to laser injury. Injured eyes (n = 5 per treatment group) were injected with 200 ng of either EED or scrambled control peptide (SCRAM), or sterile isotonic saline immediately after injury and again 7 days later. Eyes were harvested 14 days following injury and changes in CNV lesion size was assessed from flat mounts of the posterior cups using spinning disc confocal microscopy captures analyzed by software-assisted volumetric morphometry.

Results: : The EED peptide efficiently translocates inside cells cultured in vitro. Pretreatment of cultured cells with EED interfered with cytoskeletal actin remodeling. CNV lesion volume was reduced by ~80% in eyes that received EED versus SCRAM or vehicle (P < 0.05).

Conclusions: : The selective nanopeptide EED, which reversibly blocks actin and actin binding protein interactions, reduces vascular lesion size in experimentally induced CNV. Selective blockade of this vital component of cell migration may prove to be a useful avenue for future therapies designed to limit aberrant neovasularization as seen in CNV.

Keywords: choroid: neovascularization • cytoskeleton • neovascularization 

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