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Cited by 272Retinal Diseases and TreatmentsGut microbiota and healthRetinal Development and Disorders

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

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Rowan, Sheldon, Jiang, Shuhong, Korem, Tal, Szymanski, Jedrzej, Chang, Min-Lee, Szelog, Jason, Cassalman, Christa, Dasuri, Kalavathi +17 more·2017·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1702302114PMC PMC5465926
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Abstract

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.

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Authors
Rowan, S., Jiang, S., Korem, T., Szymanski, J., Chang, M.-L., Szelog, J., Cassalman, C., Dasuri, K., McGuire, C., Nagai, R., Du, X.-L., Brownlee, M., Rabbani, N., Thornalley, P. J., Baleja, J. D., Deik, A. A., Pierce, K. A., Scott, J. M., Clish, C. B., Smith, D. E., Weinberger, A., Avnit-Sagi, T., Lotan-Pompan, M., Segal, E., & Taylor, A.
Affiliations
  • Tufts University (US)
  • Weizmann Institute of Science (IL)
  • Department of Plant Sciences, Weizmann Institute of Technology, Rehovot 7610001, Israel;
  • Tokai University (JP)
  • Albert Einstein College of Medicine (US)
  • University Hospital Coventry (GB)
  • Broad Institute (US)
  • Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 7610001, Israel;
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2017-05-15
Volume
114
Issue
22
Pages
E4472-E4481
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1702302114
PMC
PMC5465926
OpenAlex
W2615974729
Cited by
272
References
16
Citations by year
2026: 24 · 2025: 29 · 2024: 33 · 2023: 32 · 2022: 40 · 2021: 38 · 2020: 25 · 2019: 25 · 2018: 21 · 2017: 5
FWCI
20.27
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/misc/userlicense.xhtml (vor, 184 d)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • HHS | NIH | National Eye Institute (RO1EY021212, RO1EY13250, RO1EY026979)
  • U.S. Department of Agriculture (58-1950-0-014, 58-1950-4-003)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Keywords
age-related macular degeneration, gut-retina axis, low glycemic index diet, retinal pigment epithelium, photoreceptor degeneration, lipofuscin accumulation, advanced glycation end products, long-chain polyunsaturated fatty acids, lipid peroxidation, gut microbiota, microbial metabolites, serotonin, Clostridiales, Bacteroidales, metabolomics, dietary intervention, aging
MeSH terms
Gastrointestinal Microbiome, Animals, Blood Glucose, Macular Degeneration, Retina, Glycation End Products, Advanced, Glycemic Index, Mice, Metabolomics, Metabolome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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