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Raffael Liegl, Zhongjie Fu, Zhongxiao Wang, Yan Gong, Ye Sun, Steven Meng, Samuel Burnim, JohnPaul SanGiovanni, Chatarina Lofqvist, Ann Hellstrom, Lois E H Smith; Adiponectin mediates dietary omega-3 long-chain polyunsaturated fatty acid protection against choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2017;58(8):815.
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© ARVO (1962-2015); The Authors (2016-present)
Neovascular age related macular degeneration (nAMD) is the most frequent cause for legal blindness in the elderly. Current treatment approaches aim to reduce the amount of macular edema and already present neovascularization.Preventative approaches have been discussed for a long time and nutrition optimization, may play a central role in these considerations.Omega 3 (ω-3) long-chain polyunsaturated fatty acids are beneficial in preventing neovascularization. Adiponectin (APN), a key metabolic regulator, mediates ω-3 driven decrease of neovascularization (NV) in the oxygen induced retinopathy model.We therefore aimed to investigate if APN may also play a role in ω-3 driven protection in two models mimicking nAMD.
Two major components of nAMD are inflammation and abberant metabolism. To account for this we used two different rodent models: Choroidal neovascularization (CNV) was caused with a laser by breaking Bruchs membrane at 4 locations on the mouse retina. Vldlr-/- mice develop neovascularization, similar to retinal angiomatous proliferations (RAP) due to impaired metabolism. Mice were put on either ω-3 or ω-6 enriched diet as control. To investigate the role of APN in these mice, we used Apn-/- mice and fed mice on either diet with APN.
C57BL/6J (WT) mice on ω-3 diet showed an improvement in the CNV model compared to ω-6 fed mice (p=0.04). Significantly larger lesions were observed in ω-3 fed Apn-/- compared to WT mice (p=0.003) but not in ω-6 fed Apn-/- when compared to WT mice (p=0.16). In Vldlr-/- mice, an ω-3 diet would reduce the number of lesions compared to ω-6 (p=0.001). In the ex-vivo choroidal sprouting model, choroids from Apn-/- showed an enlarged sprouting zone compared to WT choroids(p=0.04). We hypothesized that ω-3 increases APN, which in turn might decrease the levels of matrix metalloproteinases (Mmp) 2 and 9, leading to increased neovascularization. Mmp2 and 9 were downregulated in ω-3 fed WT mice (Mmp2:p<0.001; Mmp9:p<0.05) compared to ω-6 controls. Apn-/- mice showed no difference for either diet (Mmp2:p=0.7;Mmp9: p=0.7).
An ω-3 enriched diet reduces the severity of neovascular AMD. We show that Adiponectin is an important regulator of these effects and modulating the amount of Adiponectin may augment the beneficial effects seen in an ω-3 enriched diet in patients suffering from neovascular AMD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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