Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty Acid Protection Against Choroidal Neovascularization in Mice
Year: 2017
Type: article
Abstract: Purpose: Neovascular age-related macular degeneration (AMD) is a major cause of legal blindness in the elderly. Diets with omega3-long-chain-polyunsaturated-fatty-acid (ω3-LCPUFA) correlate with a decreased risk of AMD. Dietary ω3-LCPUFA versus ω6-LCPUFA inhibits mouse ocular neovascularization, but the underlying mechanism needs further exploration. The aim of this study was to investigate if adiponectin (APN) mediated ω3-LCPUFA suppression of neovessels in AMD. Methods: The mouse laser-induced choroidal neovascularization (CNV) model was used to mimic some of the inflammatory aspect of AMD. CNV was compared between wild-type (WT) and Apn-/- mice fed either otherwise matched diets with 2% ω3 or 2% ω6-LCPUFAs. Vldlr-/- mice were used to mimic some of the metabolic aspects of AMD. Choroid assay ex vivo and human retinal microvascular endothelial cell (HRMEC) proliferation assay in vitro was used to investigate the APN pathway in angiogenesis. Western blot for p-AMPKα/AMPKα and qPCR for Apn, Mmps, and IL-10 were used to define mechanism. Results: ω3-LCPUFA intake suppressed laser-induced CNV in WT mice; suppression was abolished with APN deficiency. ω3-LCPUFA, mediated by APN, decreased mouse Mmps expression. APN deficiency decreased AMPKα phosphorylation in vivo and exacerbated choroid-sprouting ex vivo. APN pathway activation inhibited HRMEC proliferation and decreased Mmps. In Vldlr-/- mice, ω3-LCPUFA increased retinal AdipoR1 and inhibited NV. ω3-LCPUFA decreased IL-10 but did not affect Mmps in Vldlr-/- retinas. Conclusions: APN in part mediated ω3-LCPUFA inhibition of neovascularization in two mouse models of AMD. Modulating the APN pathway in conjunction with a ω3-LCPUFA-enriched-diet may augment the beneficial effects of ω3-LCPUFA in AMD patients.
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,850
Funders: Ögonfonden, Stiftelsen Kronprinsessan Margaretas Arbetsnämnd för Synskadade, European Commission, Deutsche Forschungsgemeinschaft, Vetenskapsrådet, De Blindas Vänner, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, National Eye Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Molecular Defence Against Retinopathy of Prematurity: Diagnosis, Prevention, and Treatment, G3916677169, Neuronal guidance molecules control revascularization in retinopathy, Novel therapies to inhibit Diabetic Retinopathy, New approach to treatment of the blinding disease Retinopathy of Prematurity (ROP), Boston Intellectual and Developmental Disabilities Research Center, Intellectual and Developmental Disablities Research Center, G8956284776, G9000042107, Dietary control of angiogenesis in retinopathy models
OpenAlex ID: W2736495973