Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice
by
Alina Adriana Ivanescu 1,2,†, Patricia Fernández-Robredo 1,3,†, Henar Heras-Mulero 2,3, Luis Manuel Sádaba-Echarri 3,4, Laura García-García 1, Vanessa Fernández-García 1, Maite Moreno-Orduna 1, Aitor Redondo-Exposito 1, Sergio Recalde 1,3,*,‡ and Alfredo García-Layana 1,3,4,‡
Alina Adriana Ivanescu 1,2,†, Patricia Fernández-Robredo 1,3,†, Henar Heras-Mulero 2,3, Luis Manuel Sádaba-Echarri 3,4, Laura García-García 1, Vanessa Fernández-García 1, Maite Moreno-Orduna 1, Aitor Redondo-Exposito 1, Sergio Recalde 1,3,*,‡ and Alfredo García-Layana 1,3,4,‡
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
*
Author to whom correspondence should be addressed.
†
These authors share first authorship credit.
‡
These authors contributed equally to this work.
Nutrients 2015, 7(7), 5423-5442; https://doi.org/10.3390/nu7075229
Received: 13 May 2015 / Revised: 5 June 2015 / Accepted: 18 June 2015 / Published: 6 July 2015
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.
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Keywords:
antioxidants; choroidal neovascularisation; mouse model; anti-VEGF
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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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