title: Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice.
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.
authors.affiliation: Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain. henarheras@yahoo.es.|Department of Ophthalmology, Hospital Virgen del Camino, Servicio Navarro de Salud, Irunlarrea 4 Street, 31008 Pamplona, Spain. henarheras@yahoo.es.
authors.forename: Alina Adriana
authors.initials: AA
authors.lastname: Ivanescu
authors.affiliation: Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain. mgarcia.6@alumni.unav.es.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain. mgarcia.6@alumni.unav.es.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernández-Robredo
authors.affiliation: Department of Ophthalmology, Hospital Virgen del Camino, Servicio Navarro de Salud, Irunlarrea 4 Street, 31008 Pamplona, Spain. henarheras@yahoo.es.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain. henarheras@yahoo.es.
authors.forename: Henar
authors.initials: H
authors.lastname: Heras-Mulero
authors.affiliation: IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain. lmsadaba@unav.es.|Department of Ophthalmology Clínica Universidad de Navarra, University of Navarra, Avda Pio XII, 36, 31008 Pamplona, Spain. lmsadaba@unav.es.
authors.forename: Luis Manuel
authors.initials: LM
authors.lastname: Sádaba-Echarri
authors.affiliation: Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain. mgarcia.6@alumni.unav.es.
authors.forename: Laura
authors.initials: L
authors.lastname: García-García
authors.affiliation: Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain. vfernandez87@hotmail.es.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fernández-García
authors.affiliation: Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain. maimoreno@unav.es.
authors.forename: Maite
authors.initials: M
authors.lastname: Moreno-Orduna
authors.affiliation: Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain. aredondo.5@alumni.unav.es.
authors.forename: Aitor
authors.initials: A
authors.lastname: Redondo-Exposito
authors.affiliation: Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain. aglayana@unav.es.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain. aglayana@unav.es.
authors.forename: Sergio
authors.initials: S
authors.lastname: Recalde
authors.affiliation: Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, Irunlarrea s/n Street, Los Castaños Building 31008 Pamplona, Spain. lmsadaba@unav.es.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain. lmsadaba@unav.es.|Department of Ophthalmology Clínica Universidad de Navarra, University of Navarra, Avda Pio XII, 36, 31008 Pamplona, Spain. lmsadaba@unav.es.
authors.forename: Alfredo
authors.initials: A
authors.lastname: García-Layana
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002829:Choroid / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000178:diet therapy*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D005451:Fluorescein Angiography; D058449:Intravitreal Injections; D014975:Lutein / Q000627:therapeutic use; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008903:Minerals / Q000627:therapeutic use; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D002352:Carrier Proteins; D015525:Fatty Acids, Omega-3; D008903:Minerals; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D014815:Vitamins; C467480:vascular endothelial growth factor A, mouse; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol; D014975:Lutein
keywords: anti-VEGF; antioxidants; choroidal neovascularisation; mouse model