Purchase this article with an account.
K.M. Connor, C.M. Aderman, J. Chen, Z. Kachra, N. Salem, J.–P. SanGiovanni, E. Chew, D.A. Carper, J.–Y. Tsai, L.E. Smith; Dietary and Pharmalogic Intervention in Proliferative Retinopathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2334.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Mammals cannot naturally produce omega–3 (ω–3) fatty acids, an essential nutrients found mainly in fish oil, from the more abundant omega–6 (ω–6) fatty acids. They must rely on a dietary supply. Lipid–based molecules act as effectors of angiogenesis and inflammation; of particular effectiveness are the eicosanoids, derived from the 20 carbon long chain polyunsaturated fatty acids (LCPUFAs), through the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Dietary intake of ω–3 LCPUFAs has been demonstrated to have anti–angiogenic and anti–inflammatory consequences. Given that LCPUFA tissue status is dependent on dietary intake and the relatively low ω–3 LCPUFA intake in western diets, these nutrients are reasonable targets for proliferative retinopathy intervention therapy.
Retinopathy was induced by subjecting, litters of C57 Bl6 neonates with mothers to 75% oxygen from P7–P12 and then room air until P17 when retinas are flat mounted after FITC perfusion to fill vessels. To study the effects of ω–3 LCPUFAs on retinopathy pregnant mice were fed (from prenatal day 1) a diet enriched with ω–3 LCPUFAs or a diet elevated in ω–6 LCPUFAs. The effects of COX–2 inhibition on proliferative retinopathy was analyzed by feeding Celecoxib to nursing mouse mothers in the water (equivalent to 5mg/kg) to achieve a low dose in the pups.
There was a ∼40% reduction in retinal neovascularization and a similar significant decrease in the non–vascularized area at P17 with pups fed from mothers with an enriched ω–3 LCPUFA diet verses a ω–3 deficient diet, indicating a significant effect of ω–3 LCPUFAs on inhibition of retinopathy (P≤0.00001). In two separate experiments (n=21 and 29 respectively) low dose COX–2 inhibition was associated with ∼50% inhibition of neovascularization at P17 (P≤0.001) indicating that there is significant potential for COX inhibition to be clinically useful.
In this study we observed that elevated dietary intake of ω–3 LCPUFAs and COX–2 inhibition resulted in inhibition of proliferative retinopathy. This data suggests that COX–2 inhibition may be synergistic with ω–3 LCPUFA intake. The potential impact of this study is great since nutritional interventions are safe, inexpensive and readily put into practice.
This PDF is available to Subscribers Only