Dietary Glycemia Contributes Reversibly to Age-related Macular Degeneration and Metabolic Disease in Aged C57Bl/6J Mice Objective Consuming high glycemia diets is a risk factor for Age-related Macular Degeneration (AMD) in humans. We sought to test in aging C57Bl/6J mice whether a high glycemic index (GI) diet would lead to AMD and other metabolic changes, and if the damage is reversible. Methods: 1-year old mice were fed high or low GI diets for one year. A crossover group had their diets shifted from high to low GI at the mid-point. Retina pathology, metabolic parameters, metabolites, advanced glycation end-products, and microbiota were measured. Results: Mice fed a high GI diet developed obesity and insulin resistance. Many metabolic pathways, including tyrosine, citrate, and ascorbate pathways, and gut microbiomes showed diet-associated changes. High GI-fed mice showed loss of photoreceptor cells and retina pathology consistent with early AMD. Pathology was less prominent in mice in the low GI or crossover groups. Conclusions Chronic consumption of a high glycemia diet induces metabolic disease and AMD, which can be reversed by lowering dietary glycemia, suggesting that diet could be a primary intervention in treatment of early AMD. Funded by NIH (RO1EY012121, RO1EY13250) and USDA (1950-510000-060-01A)
A 67-year-old male patient presented with right scrotal swelling and underwent a right hydrocelectomy. A 1 cm paratesticular lesion was found within the hydrocele sac after entering the tunica vaginalis. Local excision grossly removed this in its entirety. Pathology returned as well differentiated papillary mesothelioma of the tunica vaginalis. Pathologic features and management options are discussed.
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.
