Disturbances in the cellular production of nitric oxide (NO) and superoxide (O2) can have detrimental effects on retinal vascular integrity and angiogenic signaling. This study was done to assess the affect of ω-3 polyunsaturated fatty acids (PUFAs) on angiogenic signaling and NO/superoxide production in retinal microvascular endothelial cells (RMECs).
DHA or EPA was used to treat primary RMECs for a period of 48 hours.
Scratch-wound assay was used to determine the RMEC migration, proliferation by the incorporation of BrdU, and a three-dimensional model of in vitro angiogenesis was used to determine angiogenic sprouting
DHA treatment increased nitrite and decreased superoxide production, which correlated with the displacement of eNOS from caveolar subdomains and colocalization with the negative regulator caveolin-1.
DHA significantly reduced the numbers of proliferating cells in control and VEGF-treated cultures (see Fig. 1).
The anti-proliferative effect was much more pronounced in the DHA-treated cells. AA, in contrast, had no effect on RMEC proliferation.
DHA improves NO bioavailability, decreases superoxide production, and blunts VEGF-mediated angiogenic signaling. These findings suggest a role for omega-3 PUFAs, particularly DHA, in maintaining vascular integrity while reducing pathologic retinal neovascularization.
Matesanz N, Park G, McAllister H, et al. Docosahexaenoic acid improves the nitroso-redox balance and reduces VEGF-mediated angiogenic signaling in microvascular endothelial cells. Invest Ophthalmol Vis Sci. 2010; 51(12):6815-6825.
