Retinal enrichment in omega-3 polyunsaturated fatty acids limits choroidal neovascularization

Purpose: Age-related Macular Degeneration (AMD) is the primary cause of blindness in elderly population of western countries. Prospective epidemiologic studies have reported that omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of progression to advanced AMD, and particularly to the neovascular forms. In this study, we have investigated the beneficial effects of omega-3 PUFA on choroidal neovascularization (CNV) in mice.Methods: Fat-1 mice, endogenously converting omega-6 to omega-3 PUFA, and littermate controls were used at 4 months of age. CNV was induced unilaterally in eye fundus by photocoagulation using a 532-nm laser. Confocal scanning laser ophthalmoscopy was used to evaluate CNV development after 9, 11 and 16 days post-laser. CNV area was quantified at the levels of the choroid and the retina by indocyanin green angiography (ICGA) and fluorescein angiography (FLA), respectively. Retinas were isolated in order to evaluate the fatty acid content by gas chromatography and the expression of genes involved in angiogenesis by RT-qPCR (Vegfa, Vegfr1, Vegfr2, Angpt1, Angpt2, Tgf- , Tie2, Serpin1).Results: The retinal content in omega-3 PUFA was significantly higher in fat-1 mice compared to controls whereas that of omega-6 PUFA was lower. While the levels of DHA were unchanged, those of n-3 docosapentaenoic acid (DPAn-3) and eicosapentaenoic acid (EPA) showed a 2-fold and 17-fold increase, respectively. FLA did not reveal any difference between fat-1 and controls. ICGA showed a reduction of CNV of 38% (p=0.035) and of 42% (p=0.009) in fat-1 mice when compared to controls 11 and 16 days after laser treatment, respectively. The expression of genes involved in angiogenesis, including Vegfa, Vegfr2 and Angpt2, was significantly lowered in the laser-treated retinas of fat-1 mice compared to controls.Conclusions: These results suggest that enriching the retina with omega-3 PUFAs may protect against the development of pathological angiogenesis. Our data are in accordance with human prospective studies suggesting that a higher dietary consumption of omega-3 PUFA reduce the risk for developing neovascular AMD.