Elastin-mediated choroidal endothelial cell migration: possible role in age-related macular degeneration

Jessica M Skeie; Robert F Mullins

doi:10.1167/iovs.08-1984

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Elastin-mediated choroidal endothelial cell migration: possible role in age-related macular degeneration

Journal article

Open access

Peer reviewed

Elastin-mediated choroidal endothelial cell migration: possible role in age-related macular degeneration

Jessica M Skeie and Robert F Mullins

Investigative ophthalmology & visual science, Vol.49(12), pp.5574-5580

12/2008

DOI: 10.1167/iovs.08-1984

PMCID: PMC2609900

PMID: 18708613

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Abstract

Endothelial cell (EC) migration is a key event in angiogenesis, and is likely to play an important role in choroidal neovascularization in age-related macular degeneration (AMD). Altered elastin metabolism has been described in AMD, and the present study sought to determine the effects of elastin-derived peptides (EDPs) on choroidal EC migration and proliferation. Migration of the chorioretinal EC line Rf/6a and a primary culture of human choroidal ECs through polycarbonate membrane inserts was quantified in the presence of elastin bioactive hexapeptides (BPs), EDPs, bovine serum albumin (BSA), or balanced salt solution. Proliferation assays and in vitro wound closure experiments were also performed in the presence of elastin fragments or balanced salt solution (control). Elastin overlay experiments were performed on sections of human eyes. For both Rf/6a and human primary choroidal ECs exposed to EDPs or BPs, the number of ECs that migrated through the polycarbonate membrane was significantly higher than ECs exposed to balanced salt solution alone or to BSA (P < 0.05) in all experiments. In contrast, the rate of EC proliferation did not significantly change in comparison to controls. Elastin binding sites were identified on choroidal ECs in human eyes. Elastin fragments increase choroidal EC migration, whereas they do not appear to increase or decrease EC proliferation. Local or systemic abnormalities in elastin physiology may participate in pathologic neovascular membrane formation in AMD.

Endothelium, Vascular - cytology

Cell Line

Elastin - metabolism

Microscopy, Electron, Scanning

Humans

Choroid - blood supply

Elastin - pharmacology

Peptide Fragments - pharmacology

Immunoenzyme Techniques

Endothelium, Vascular - physiology

Endothelium, Vascular - ultrastructure

Cell Movement - drug effects

Macular Degeneration - metabolism

Choroidal Neovascularization - metabolism

Choroidal Neovascularization - pathology

Cell Proliferation - drug effects

Binding Sites

Wound Healing - drug effects

Macular Degeneration - pathology

Details

Title: Subtitle: Elastin-mediated choroidal endothelial cell migration: possible role in age-related macular degeneration
Creators: Jessica M Skeie - Center for Macular Degeneration, Department of Ophthalmology and Visual Science, University of Iowa, Iowa City, Iowa 52242, USA
Robert F Mullins
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.49(12), pp.5574-5580
DOI: 10.1167/iovs.08-1984
PMID: 18708613
PMCID: PMC2609900
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 EY017451-02 / NEI NIH HHS EY017451 / NEI NIH HHS R01 EY017451 / NEI NIH HHS F32 EY022280 / NEI NIH HHS
Language: English
Date published: 12/2008
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980041702771

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