Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration
| Autor: | Maya Lotan-Pompan, Jedrzej Szymanski, Tal Korem, Naila Rabbani, Kerry A. Pierce, Adina Weinberger, Justin M. Scott, Christa Cassalman, Allen Taylor, Tali Avnit-Sagi, Xue Liang Du, Amy Deik, Eran Segal, Christina McGuire, Jason Szelog, Michael Brownlee, Shuhong Jiang, Sheldon Rowan, Kalavathi Dasuri, Donald Smith, Min Lee Chang, Paul J. Thornalley, James D. Baleja, Clary B. Clish, Ryoji Nagai |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Blood Glucose Glycation End Products Advanced medicine.medical_specialty genetic structures Gut flora Retina 03 medical and health sciences chemistry.chemical_compound Macular Degeneration Mice Atrophy Glycation Internal medicine medicine Metabolome Animals Metabolomics Multidisciplinary biology Retinal Macular degeneration biology.organism_classification medicine.disease eye diseases Gastrointestinal Microbiome 030104 developmental biology Glycemic index Endocrinology chemistry PNAS Plus Glycemic Index Advanced glycation end-product sense organs |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 114(22) |
| ISSN: | 1091-6490 |
| Popis: | Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not. Critically, switching from the HG to the LG diet late in life arrested or reversed AMDf. LG diets limited the accumulation of advanced glycation end products, long-chain polyunsaturated lipids, and their peroxidation end-products and increased C3-carnitine in retina, plasma, or urine. Untargeted metabolomics revealed microbial cometabolites, particularly serotonin, as protective against AMDf. Gut microbiota were responsive to diet, and we identified microbiota in the Clostridiales order as being associated with AMDf and the HG diet, whereas protection from AMDf was associated with the Bacteroidales order and the LG diet. Network analysis revealed a nexus of metabolites and microbiota that appear to act within a gut–retina axis to protect against diet- and age-induced AMDf. The findings indicate a functional interaction between dietary carbohydrates, the metabolome, including microbial cometabolites, and AMDf. Our studies suggest a simple dietary intervention that may be useful in patients to arrest AMD. |
| Databáze: | OpenAIRE |
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