Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration

Sheldon Rowan, Shuhong Jiang, Tal Korem, Jedrzej Szymanski, Min Lee Chang, Jason Szelog, Christa Cassalman, Kalavathi Dasuri, Christina McGuire, Ryoji Nagai, Xue Liang Du, Michael Brownlee, Naila Rabbani, Paul J. Thornalley, James D. Baleja, Amy A. Deik, Kerry A. Pierce, Justin M. Scott, Clary B. Clish, Donald E. SmithAdina Weinberger, Tali Avnit-Sagi, Maya Lotan-Pompan, Eran Segal, Allen Taylor

Research output: Contribution to journalArticlepeer-review

142 Scopus citations


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- A nd 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.

Original languageEnglish (US)
Pages (from-to)E4472-E4481
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number22
StatePublished - May 30 2017


  • Advanced glycation end-product
  • Age-related macular degeneration
  • Glycemic index
  • Gut microbiome
  • Metabolomics

ASJC Scopus subject areas

  • General


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