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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 213505, 11 pages
Research Article

Effect of Lutein and Antioxidant Supplementation on VEGF Expression, MMP-2 Activity, and Ultrastructural Alterations in Apolipoprotein E-Deficient Mouse

1Experimental Ophthalmology Laboratory, Clínica Universidad de Navarra, School of Medicine, University of Navarra, ES-31008 Pamplona, Spain
2Department of Ophthalmology, Clínica Universidad de Navarra, School of Medicine, University of Navarra, Pio XII 36, ES-31008 Pamplona, Spain
3Atherothrombosis Research Laboratory, Division of Cardiovascular Sciences, Center for Applied Medical Research (CIMA), University of Navarra, ES-31008 Pamplona, Spain

Received 7 February 2013; Revised 5 April 2013; Accepted 8 April 2013

Academic Editor: Kota V. Ramana

Copyright © 2013 Patricia Fernández-Robredo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Oxidative stress is involved in the pathogenesis of several diseases such as atherosclerosis and age-related macular degeneration (AMD). ApoE-deficient mice (apoE−/−) are a well-established model of genetic hypercholesterolemia and develop retinal alterations similar to those found in humans with AMD. Thus supplementation with lutein or multivitamin plus lutein and glutathione complex (MV) could prevent the onset of these alterations. ApoE−/− mice ( , 3 months old) were treated daily for 3 months with lutein (AE-LUT) or MV (two doses): AE-MV15 (15 mg/kg/day) and AE-MV50 (50 mg/kg/day) and were compared to controls with vehicle (AE-C). Wild-type mice ( ) were also used as control (WT-C). ApoE−/− mice showed higher retinal lipid peroxidation and increased VEGF expression and MMP-2 activity, associated with ultrastructural alterations such as basal laminar deposits, vacuoles, and an increase in Bruch's membrane thickness. While lutein alone partially prevented the alterations observed in apoE−/− mice, MV treatment substantially reduced VEGF levels and MMP-2 activity and ameliorated the retinal morphological alterations. These results suggest that oxidative stress in addition to an increased expression and activity of proangiogenic factors could participate in the onset or development of retinal alterations of apoE−/− mice. Moreover, these changes could be prevented by efficient antioxidant treatments.