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Nutrients 2015, 7(7), 5423-5442; doi:10.3390/nu7075229

Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice

1
Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain
2
Department of Ophthalmology, Hospital Virgen del Camino, Servicio Navarro de Salud, Irunlarrea 4 Street, 31008 Pamplona, Spain
3
IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
4
Department of Ophthalmology Clínica Universidad de Navarra, University of Navarra, Avda Pio XII, 36, 31008 Pamplona, Spain
These authors share first authorship credit.
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 13 May 2015 / Revised: 5 June 2015 / Accepted: 18 June 2015 / Published: 6 July 2015
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Abstract

We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. View Full-Text
Keywords: antioxidants; choroidal neovascularisation; mouse model; anti-VEGF antioxidants; choroidal neovascularisation; mouse model; anti-VEGF
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. (CC BY 4.0).

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MDPI and ACS Style

Ivanescu, A.A.; Fernández-Robredo, P.; Heras-Mulero, H.; Sádaba-Echarri, L.M.; García-García, L.; Fernández-García, V.; Moreno-Orduna, M.; Redondo-Exposito, A.; Recalde, S.; García-Layana, A. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice. Nutrients 2015, 7, 5423-5442.

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