Effects of antioxidant components of AREDS vitamins and zinc ions on endothelial cell activation: implications for macular degeneration

Shemin Zeng; Jasmine Hernández; Robert F Mullins

doi:10.1167/iovs.11-8531

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Effects of antioxidant components of AREDS vitamins and zinc ions on endothelial cell activation: implications for macular degeneration

Journal article

Open access

Peer reviewed

Effects of antioxidant components of AREDS vitamins and zinc ions on endothelial cell activation: implications for macular degeneration

Shemin Zeng, Jasmine Hernández and Robert F Mullins

Investigative ophthalmology & visual science, Vol.53(2), pp.1041-1047

02/2012

DOI: 10.1167/iovs.11-8531

PMCID: PMC3317404

PMID: 22247465

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https://doi.org/10.1167/iovs.11-8531View

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Abstract

To investigate whether the benefit of Age-Related Eye Disease Study (AREDS) formula multivitamins and zinc in the progression of age-related macular degeneration (AMD) may occur through inhibiting inflammatory events in the choroid. Mouse C166 endothelial cells (ECs) and, for some experiments, human retinal pigment epithelium (RPE)-choroid organ cultures were treated with AREDS multivitamin solution (MVS) or ZnCl(2). The cytotoxicity of MVS was evaluated using a lactate dehydrogenase colorimetric assay. Cell motility was assessed using a scratch assay. Macrophage adhesion to EC monolayers or ICAM-1 protein was determined after MVS and zinc treatment and with or without lipopolysaccharide (LPS). Quantitative reverse transcription PCR and Western blot analysis were used to determine the effects of MVS on the expression of proinflammatory molecules in treated and untreated cells. AREDS MVS and zinc did not affect C166 EC viability until the 56th hour after treatment. Scratch assays showed partial inhibition of MVS and zinc on EC migration. In cell adhesion assays, MVS and zinc decreased the number of macrophages bound to EC and to ICAM-1 protein. Quantitative PCR showed that LPS increased the expression of ICAM-1 in both C166 and human RPE-choroid cultures, which was partially offset by MVS and zinc. MVS and zinc also mitigated LPS-induced ICAM-1 protein expression on Western blot analysis. Treatment with AREDS MVS and zinc may affect both angiogenesis and endothelial-macrophage interactions. These results suggest that AREDS vitamins and zinc ions may slow the progression of AMD, in part through the attenuation of EC activation.

Macrophages - physiology

Neovascularization, Physiologic - drug effects

Endothelial Cells - metabolism

Humans

Endothelium, Vascular - drug effects

Antioxidants - pharmacology

Trace Elements - pharmacology

Cell Adhesion - drug effects

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Macular Degeneration - drug therapy

Vitamins - pharmacology

Cell Movement - drug effects

Intercellular Adhesion Molecule-1 - metabolism

Animals

Intercellular Adhesion Molecule-1 - drug effects

Choroid - immunology

Macrophages - drug effects

Mice

Zinc - pharmacology

Dietary Supplements

Choroid - drug effects

Endothelial Cells - drug effects

Details

Title: Subtitle: Effects of antioxidant components of AREDS vitamins and zinc ions on endothelial cell activation: implications for macular degeneration
Creators: Shemin Zeng - Department of Ophthalmology and Visual Sciences, Institute for Vision Research, The University of Iowa, Iowa City, Iowa 52242, USA
Jasmine Hernández
Robert F Mullins
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.53(2), pp.1041-1047
Publisher: United States
DOI: 10.1167/iovs.11-8531
PMID: 22247465
PMCID: PMC3317404
ISSN: 0146-0404
eISSN: 1552-5783
Grant note: R01 EY017451 / NEI NIH HHS
Language: English
Date published: 02/2012
Academic Unit: Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9983980035802771

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