PREVENTIVE EFFECT OF A NUTRITIONAL SUPPLEMENT WITH RESVERATROL AND DHA IN CNV LASER-INDUCED MODEL

Abstract

Purpose: We aimed to investigate the effect of Resvega (nutritional complex with omega-3 and resveratrol) in the prevention of the onset of CNV in a murine model of laser-induced CNV. In addition, we wanted to elucidate the effect of this therapy combined with anti-vascular endothelial growth factor (VEGF). We hypothesize that the combined effect of these substances could act as a preventive therapy, avoiding late complications of retinal pathologies such as choroidal neovascularisation (CNV).

Methods: Sixty C57BL6/J mice underwent a diode laser-induced CNV model, and were divided into 4 groups (n=15): Control group: vehicle by oral gavage. R group: daily oral Resvega (R). C-VEGF group: oral vehicle and intravitreal anti-VEGF. R-VEGF group: oral R and and intravitreal anti-VEGF. Oral treatments (100 µL) were administered ten days before laser until 28 days post-laser and intravitreal injections (7 µl) were performed 48 hours after laser. CNV evolution was assessed weekly through fluorescein angiography (FA) for 4 weeks. CD-31 immunofluorescence was assessed in choroidal flat mounts after sacrifice. Gene and protein expression of VEGF was analyzed with RT-PCR and western-blot, respectively. Results were statistically analyzed with SPSS 15.0 software.

Results: The FA leakage area was significantly reduced in both R groups compared with V group (R group, p<0.001 and R+ anti VEGF group, p<0.05). CNV lesion size results also showed an important reduction when comparing the V group with R group (p<0.01) and with R+ anti VEGF (p<0.05). Moreover, RT-PCR and western-blot analysis showed a significant decrease in VEGF expression in R and R-VEGF groups (p<0.05).

Conclusions: In conclusion, this is the first study that combines resveratrol and omega-3 to investigate the potential preventive effect on CNV lesions. Our work shows that Resvega can prevent the CNV induced lesions size as well as reduce VEGF gene and protein expression in this mice model. In addition, therapeutic effect of anti-VEGF treatment was masked with the Resvega protective effect and a synergistic effect with anti-VEGF therapy could not be observed.

Keywords: 700 retinal neovascularization • 748 vascular endothelial growth factor