Dietary -3 Polyunsaturated Fatty Acids Reverse Late Stage Pathologic Retinal Neovascularization

Abstract

Purpose: : Retinal neovascularization, a prevalent cause of blindness and is characterized by two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. Our previous studies demonstrated that a lifelong ω-3 versus an ω-6 PUFA diet protected mice from oxygen-induced retinopathy by preventing neovascularization through revascularization of hypoxic retina. While long term treatment with dietary ω-3 PUFAs is clearly beneficial in preventing retinopathy it remains unclear what effect late stage treatment with dietary ω-3 PUFAs would have on reversing retinal neovascularization. Our initial study showed that during the vessel loss phase of the disease (when mice are in high oxygen) dietary intake had no effect on vessel loss.

Methods: : In the oxygen-induced retinopathy model, C57Bl/6 mothers were fed (from postnatal day 0 (P0)) a diet enriched with ω-3 PUFA or a diet elevated in ω-6 PUFA. ω PUFA composition of the milk from the mothers reflected their diet. Alternatively, mice were treated with an ω-3 PUFA or ω-6 PUFA diet at P12 or P15, after the initial vessel loss phase of oxygen-induced retinopathy. We then analyzed the role these diets played in reversing late stage disease. Retinal RNA was also isolated for real-time PCR analysis.

Results: : As seen previously, mice on a lifelong ω-3 (versus ω-6) enriched PUFA diet had a significant increase in vessel re-growth as well as diminished neovascularization and a decrease in both macrophage markers and associated inflammatory molecules. In mice given the diets after vessel loss, no change in vessel re-growth (vaso-obliteration) was observed at P17. However, mice on a ω-3 PUFA diet were significantly protected (~50%) from the pathological neovascular stage of the disease compared to their ω-6 PUFA fed counterparts. Here no change in macrophage markers was observed. However in the ω-3 PUFA fed mice there was a significant decrease (40%) in inflammatory molecules.

Conclusions: : This data indicates that ω-3 PUFAs can reverse the pathological neovascularization phase of retinopathy after it has been initiated this is associated with a dampening of the inflammatory response.

Keywords: retinal neovascularization • lipids • inflammation